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How much does IVF cost?

Woodcock S, 2025·GoodRx

Is termination of a desired pregnancy due to possible fetal abnormalities a case of moral injury? A preliminary report

Sartel-Raviv S et al., 2025·Death studies

Termination of pregnancy (TOP) due to possible fetal abnormalities is known to be associated with various mental health problems. This study examines associations between potentially morally injurious events (PMIEs), moral injury outcomes (MI), posttraumatic stress disorder (PTSD), and prolonged grief (PG) among treatment-seeking women following late pregnancy loss. A volunteer sample of (n = 132) Israeli women who attended a reproductive psychiatry clinic following TOP (n = 99) or pregnancy loss due to intrauterine fetal demise (IUFD; n = 33), responded to self-report questionnaires in a cross-sectional, comparative study. Results show that among participants in the TOP group, PMIEs-self predicted MI outcomes of shame, and PMIEs-betrayal predicted MI outcomes of trust violation. Importantly, following exposure to PMIE-self, MI outcomes of trust violation significantly predicted both PTSD and PG symptoms. This study emphasized that TOP due to possible fetal abnormalities, may constitute a morally injurious experience, highlighting the need for clinical interventions addressing MI.

Endometriosis Quality of Life Cohort Study: Long-term Impact of Radical Laparoscopic Excision of Endometriosis

McDonnell R et al., 2025·Gynecology and minimally invasive therapy

Semen quality and lifespan: a study of 78,284 men followed for up to 50 years

Priskorn L et al., 2025·Human Reproduction

The pathogenesis, diagnosis, and treatment of chronic endometritis: a comprehensive review

Yan X et al., 2025·Frontiers in endocrinology

Chronic endometritis (CE) is a subtle but persistent inflammatory disorder of the endometrium that is often underdiagnosed due to its asymptomatic or non-specific presentation. The etiology of CE primarily involves microbial infections and immune dysregulation, often accompanied by microbial dysbiosis. Diagnosis relies on histopathological examination, especially the identification of stromal plasma cells, alongside hysteroscopic findings and microbiological testing, though standardization remains lacking. Mechanistically, CE-induced infertility stems from altered immune cell profiles, impaired endometrial receptivity, aberrant decidualization, dysbiosis of the endometrial microbiota, and abnormal uterine peristalsis. Aberrant gene expression and hormone receptor dysregulation further disrupt the implantation window. This review summarizes current understanding of the diagnostic criteria, pathogenic mechanisms, and therapeutic strategies for CE, emphasizing its crucial role in infertility and the need for standardized clinical management.

International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2019

Dyer S et al., 2025·Fertility and Sterility

ICMART world report on global assisted reproductive technology activity in 2019. Reports utilization, effectiveness, and safety data submitted from national and regional registries worldwide. Pre-pandemic activity baseline. Dyer S, Chambers GM, Jwa SC, Baker VL, Banker M, de Mouzon J, Elgindy E, Fu B, Ishihara O, Kupka M, Zegers-Hochschild F, Adamson GD.

Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization

Winstanley YE et al., 2025·Nature Communications

The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known. We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O2 or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres apparent in the pluripotent Inner Cell Mass (ICM) and persisting after organogenesis. Identical defects of elevated mtROS in zygotes followed by impaired telomere elongation, occurred with maternal obesity or advanced age. We further demonstrate that telomere elongation during ICM formation is controlled by mitochondrial-nuclear communication at fertilization. Using mitochondrially-targeted therapeutics (BGP-15, MitoQ, SS-31, metformin) we demonstrate that it is possible to modulate the preimplantation telomere resetting process and restore deficiencies in neonatal telomere length.

Relationship between chronic endometritis and fallopian tube obstruction and its influence on pregnancy outcome after fallopian tubal recanalization

Sun Y et al., 2024·Ther Adv Reprod Health

Chronic endometritis (CE), frequently asymptomatic, is associated with female infertility. Fallopian tube obstruction (FTO) is also one of the factors contributing to female infertility. More than 90% of cases of proximal FTO can be successfully treated after fallopian tubal recanalization (FTR) and the spontaneous pregnancy rate of treated women after FTR is only about 30%. Potential factors affecting the success rate of FTR remain unclear. We speculate that CE may be one of the reasons affecting the recanalization of the fallopian tubes. To identify the correlation between CE and FTO, as well as the influence of CE on pregnancy outcomes following FTR. Retrospective observational study. We retrospectively analyzed 498 women of childbearing age who underwent laparoscopy and hysteroscopy surgery for infertility. Endometrial samples were collected during surgery for CD138 immunohistochemistry staining for the diagnosis of CE. Based on the results of the tubal patency test, they the fallopian tubal patency group and the proximal FTO group. The prevalence of CE was compared between these two groups. All women with FTO underwent FTR during the operation until successful treatment was achieved. Pregnancy outcomes were assessed after a 12-month follow-up period following the procedures. Logistic regression was used to analyze factors that might affect pregnancy after FTR. The prevalence of CE in women with tubal obstruction was 30.5%, which was significantly higher than that in the fallopian tubal patency group (10.75%), p < 0.001. After FTR, the prevalence of CE in non-pregnant women was 40.18%, which was higher than that in pregnant women (40.18% vs 13.11%), and the difference was significant (p < 0.001). Multiple regression analysis showed that CE was a significant risk factor for FTO (OR: 2.54, 95% CI: 1.368-4.717, p < 0.05). In addition, CE was identified as a risk factor for infertility after FTR (OR: 4.730, 95% CI: 2.012-11.122). The presence of CE seems to decrease the likelihood of achieving spontaneous pregnancy following FTR. This observation underscores the clinical importance of early detection and treatment of CE, emphasizing the necessity for immediate intervention to prevent potential fertility complications.

Endometriosis and Ovarian Cancer-Reply

Schliep KC et al., 2024·JAMA

Validation of administrative health data for the identification of endometriosis diagnosis

Kiser AC et al., 2024·Hum Reprod

How do endometriosis diagnoses and subtypes reported in administrative health data compare with surgically confirmed disease? For endometriosis diagnosis, we observed substantial agreement and high sensitivity and specificity between administrative health data-International Classification of Diseases (ICD) 9 codes-and surgically confirmed diagnoses among participants who underwent gynecologic laparoscopy or laparotomy. Several studies have assessed the validity of self-reported endometriosis in comparison to medical record reporting, finding strong confirmation. We previously reported high interand intra-surgeon agreement for endometriosis diagnosis in the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study. STUDY DESIGN, SIZE, In this validation study, participants (n = 412) of the Utah operative cohort of the ENDO Study (2007-2009) were linked to medical records from the Utah Population Database (UPDB) to compare endometriosis diagnoses from each source. The UPDB is a unique database containing linked data on over 11 million individuals, including statewide ambulatory and inpatient records, state vital records, and University of Utah Health and Intermountain Healthcare electronic healthcare records, capturing most Utah residents. PARTICIPANTS/MATERIALS, SETTING, The ENDO operative cohort consisted of individuals aged 18-44 years with no prior endometriosis diagnosis who underwent gynecologic laparoscopy or laparotomy for a variety of surgical indications. In total, 173 women were diagnosed with endometriosis based on surgical visualization of disease, 35% with superficial endometriosis, 9% with ovarian endometriomas, and 14% with deep infiltrating endometriosis. Contemporary administrative health data from the UPDB included ICD diagnostic codes from Utah Department of Health in-patient and ambulatory surgery records and University of Utah and Intermountain Health electronic health records. MAIN For endometriosis diagnosis, we found relatively high sensitivity (0.88) and specificity (0.87) and substantial agreement (Kappa [Κ] = 0.74). We found similarly high sensitivity, specificity, and agreement for superficial endometriosis (n = 143, 0.86, 0.83, Κ = 0.65) and ovarian endometriomas (n = 38, 0.82, 0.92, Κ = 0.58). However, deep infiltrating endometriosis (n = 58) had lower sensitivity (0.12) and agreement (Κ = 0.17), with high specificity (0.99). LIMITATIONS, Medication prescription data and unstructured data, such as clinical notes, were not included in the UPDB data used for this study. These additional data types could aid in detection of endometriosis. Most participants were white or Asian with Hispanic ethnicity reported 11% of the time, which may limit generalizability to some US states. Additionally, given that participants whose administrative health records we utilized were also part of the ENDO Study, the surgeons may have been more vigilant in diagnostic coding due to the operative forms they completed for the ENDO Study, which may have led to increased validity. However, the codes compared in the UPDB would have been entered by medical coders as part of standard clinical practice. We observed substantial agreement between administrative health data and surgically confirmed endometriosis diagnoses overall, and for superficial and ovarian endometrioma subtypes. These findings may provide reassurance to researchers using administrative healthcare records to assess risk factors and long-term health outcomes of endometriosis. Our findings corroborate prior research that demonstrates high specificity but low sensitivity for deep infiltrating endometriosis, indicating deep infiltrating endometriosis is not reliably annotated in administrative healthcare data. This suggests that medical record-based deep infiltrating endometriosis diagnoses may be suitable for etiologic studies but not for surveillance or detection studies. STUDY FUNDING/COMPETING INTEREST(S): The original ENDO Study was funded by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contracts NO1-DK-6-3428; NO1-DK-6-3427; 10001406-02). We acknowledge partial support for the UPDB through grant P30 CA2014 from the National Cancer Institute, University of Utah and from the University of Utah's program in Personalized Health and Center for Clinical and Translational Science. This research was also supported by the NCRR grant, 'Sharing Statewide Health Data for Genetic Research' (R01 RR021746, G. Mineau, PI) with additional support from the Utah Department of Health and Human Services, University of Utah. Additionally, this research was supported by the Utah Cancer Registry, which is funded by the National Cancer Institute's SEER Program, Contract No. HHSN261201800016I, the US Centers for Disease Control and Prevention's National Program of Cancer Registries, Cooperative Agreement No. NU58DP007131, with additional support from the University of Utah and Huntsman Cancer Foundation. Research reported in this publication was also supported by the National Institutes of Health (Award Numbers R01HL164715 [to L.V.F., K.C.S., and A.Z.P.] and K01AG058781 [to K.C.S.]), by the Huntsman Cancer Institute's Breast and Gynecologic Cancers Center, and by the Doris Duke Foundation's COVID-19 Fund to Retain Clinical Scientists funded by the American Heart Association. A.C.K. was supported by Training Grant Number 5T15LM007124 from the National Library of Medicine to K.E. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other sponsors. There are no competing interests among any of the authors. N/A.

Lab-based semen parameters as predictors of long-term health in men-a systematic review

Nedelcu S et al., 2024·Hum Reprod Open

Can semen parameters predict long-term health outcomes in men? There is a lack of evidence to suggest a higher risk of comorbidities in men with poor semen concentration. Male infertility has been long associated with a higher mortality risk and possibly higher chance of developing comorbidities but there has been less focus on semen analysis as a potential predictive factor. We searched PubMed/MEDLINE, EMBASE, and EBM databases from inception to December 2023. heading 1 ('OR', semen analysis, sperm count, sperm parameter*, male infertility, azoospermia, aspermia, oligospermia, teratozoospermia, asthenozoospermia) 'AND' heading 2 ('OR', morbidity, mortality, diabetes, cancer, cardiovascular, death, hypertension, stroke, long-term health). We included all studies that analyzed the risk of mortality and/or future development of comorbidities in men with at least one semen analysis. Case series and reviews were excluded. A narrative synthesis was done for all studies and meta-analysis where possible. Odds ratio (ORs) (95% CI, P-value) were calculated for all men with one suboptimal semen parameter and associated with the risk of a particular outcome. The risk of bias was assessed with QUADAS-2. MAIN Twenty-one studies were finally included. There was either a high or unclear risk of bias in all studies. The results only allowed for meta-analysis on categories of sperm concentration. We found a 2-fold increase in mortality risk in azoospermic men compared to oligospermic (OR 1.96, 95% CI: 1.29-2.96) and normozoospermic (OR 2.00, 95% CI: 1.23-3.25) groups, but not in oligospermic compared to normozoospermic (OR 1.04, 95% CI: 0.52-2.09). There was no difference in risk of cardiovascular disease in any of the sperm concentration groups (azoospermic-oligospermic OR 0.94, 95% CI: 0.74-1.20, azoospermic-normozoospermic OR 1.11, 95% CI: 0.71-1.75, and oligospermic-normozoospermic OR 1.12, 95% CI: 0.80-1.55). OR for diabetes in azoospermic men was higher only compared to oligospermic (OR 2.16, 95% CI: 1.55-3.01). The risk of all-site cancer was higher in azoospermic men compared to oligospermic (OR 2.16, 95% CI: 1.55-3.01) and normozoospermic (OR 2.18, 95% CI: 1.20-3.96). Only azoospermic men might be at higher risk of testicular cancer when compared to men with normal sperm concentration (OR 1.80, 95% CI: 1.12-2.89). LIMITATIONS Although our pooled analysis shows an increased risk of mortality and all-site cancer risk in azoospermic men, the results show a lack of evidence to suggest a higher risk of comorbidities in men with poor semen concentration. Given the limited available data, the nature of the studies, and the high risk of bias, the results should be interpreted with caution. There is not enough data to confirm the usability of semen analysis as a predictor of poor long-term health in men, especially within the general population. No funding was obtained for this study. A.M. has received funding from Merck Serono, Ferring, Gedeon Richter, Pharmasure, and Cook Medical to attend medical conferences; has been a participant in an advisory board for Ferring; and has given an invited lecture for a Merck Serono advisory board. S.N. has received funding for medical conference attendance from Ferring and Cook Medical. PROSPERO No. CRD42024507563.

Current surgical treatment of uterine isthmocele: an update of existing literature

Stavridis K et al., 2024·Arch Gynecol Obstet

The prevalence of uterine isthmocele, also known as a uterine niche, has risen in parallel with increasing cesarean section (CS) rates, affecting approximately 60% of women depending on their history of cesarean deliveries. This condition, now categorized as cesarean scar disorder (CSD) by the "Delphi consensus," is characterized by one primary or two secondary symptoms. Diagnosis can be made through transvaginal ultrasound, sonohysterography, hysteroscopy, or magnetic resonance imaging (MRI). Management of isthmocele may involve pharmacological or surgical interventions. This review aims to provide a thorough analysis of the surgical management options, focusing on postoperative symptom relief, intraoperative and postoperative complications, length of hospital stay, and impact on secondary infertility. PubMed was comprehensively searched for observational studies from inception to 07.08.2024. Surgical treatments include hysteroscopic resection, laparoscopic procedures, and vaginal approaches, all of which offer comparable symptom relief. However, the vaginal approach is associated with a longer hospital stay. The robotic-assisted approach shows promising results but lacks extensive data. Among surgical options, hysteroscopic treatment has the fewest complications but is generally avoided when residual myometrial thickness (RMT) is less than 3 mm. While many CSDs remain asymptomatic, and some women with uterine isthmocele may not wish to conceive, symptomatic patients or those desiring to conceive may benefit from surgical intervention. The choice of procedure should be based on individual patient characteristics, particularly RMT, to define the most appropriate surgical approach.

Maternal use of hormonal contraception and risk of childhood leukemia: A Scandinavian population-based cohort study

Hemmingsen CH et al., 2024·Eur J Cancer

Maternal hormonal contraception use has been associated with childhood leukemia risk. However, studies are few and often based on self-reported information. Using registry data from Denmark, Norway, and Sweden, we identified 3,183,316 children (born 1996-2018) and followed them from birth until leukemia diagnosis, censoring (death, emigration, other cancer, 20th birthday) or study closure (December 31st, 2017, 2018 or 2020). We estimated hazard ratios (HRs) and 95 % confidence intervals (CIs) for childhood leukemia (any, lymphoid and non-lymphoid) associated with maternal recent use (≤ 3 months before or during pregnancy) or previous use (before recent use) of hormonal contraception overall and by type, compared to no use. During 29,455,528 person-years, 1701 children developed leukemia (no 518, 974, 209). Maternal recent use of hormonal contraception was associated with an increased leukemia risk in children (HR 1.22, 95 % CI 1.04-1.44; incidence rate per 1,000,000 person-years [IR] 65), compared to no use (IR 53). The association was strongest for non-lymphoid leukemia (HR 1.69, 95 % CI 1.20-2.37) and mainly driven by the oral combined products, both for any leukemia (HR 1.29, 95 % CI 1.05-1.59) and non-lymphoid leukemia (HR 1.75, 95 % CI 1.17-2.62). Additionally, non-lymphoid leukemia was associated with recent use of the non-oral progestin-only products (HR 2.10, 95 % CI 1.28-3.44). Although the absolute risk was low, maternal hormonal contraception use up to or during pregnancy was associated with an increased childhood leukemia risk, particularly non-lymphoid leukemia, and mainly driven by oral combined and non-oral progestin-only products.

Editorial: Opportunities and challenges of human preconception research

Kahn LG et al., 2024·Front Reprod Health

Evidence-based guideline: premature ovarian insufficiency

Panay N et al., 2024·Hum Reprod Open

How should premature/primary ovarian insufficiency (POI) be diagnosed and managed based on the best available evidence from published literature?Summary answerThe current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae, and treatment of POI. Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular, and cognitive health. Although hormone therapy (HT) can mitigate some of these effects, many questions still remain regarding the optimal management of POI.Study design size durationThe guideline was developed according to the structured methodology for development of ESHRE guidelines. Key questions were determined by a group of experts and informed by a scoping survey of women and health care professionals. Literature searches and assessments were then performed. Papers published up to 30 January 2024 and written in English were included in the guideline. An integrity review was conducted for the randomized controlled trials (RCTs) on POI included in the guideline. Participants/materials setting methodsBased on the collected evidence, recommendations were formulated and discussed within the guideline development group until consensus was reached. Women with lived experience of POI informed the recommendations in general, and particularly on those on provision of care. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline development group and the ESHRE Executive Committee. s and the role of chanceNew data indicate a higher prevalence of POI, 3.5%, than was previously thought. This guideline aims to help health care professionals to apply best practice care for women with POI. The recent update of the POI guideline covers 40 clinical questions on diagnosis of the condition, the different sequelae, including bone, cardiovascular, neurological and sexual function, fertility and general well-being, and treatment options, including HT. The list of clinical questions was expanded from the previous iteration of the guideline (2015) based on the scoping survey and appreciation of emerging knowledge of POI. Questions were added on the role of anti-Müllerian hormone (AMH) in the diagnosis of POI, fertility preservation, muscle health, and specific considerations for HT in iatrogenic POI. Additionally, the topic on complementary treatments was extended with specific focus on non-hormonal treatments and lifestyle management options. Significant changes from the previous 2015 guideline include the recommendations that only one elevated FSH >25 IU is required for diagnosis of POI, and guidance that AMH testing, repeat FSH measurement, and/or AMH may be required where there is diagnostic uncertainty. Recommendations were also updated regarding genetic testing, estrogen doses and regimens, use of the combined oral contraceptive and testosterone therapy. Women with lived experience of POI informed the recommendations on provision of care. Limitations reasons for cautionThe guideline describes different management options, but it must be acknowledged that for most of these options, supporting evidence is limited for POI. s of the findingsThe guideline provides health care professionals with clear advice on best practice in POI care, based on the best evidence currently available. In addition, a list of research recommendations is provided to guide further studies in POI.Study funding/competing interestsThe guideline was developed and funded by ESHRE, American Society for Reproductive Medicine (ASRM), Centre for Research Excellence in Women's Health in Reproduction Life (CRE-WHiRL), and International Menopause Society (IMS), covering expenses associated with the guideline meetings, literature searches, and dissemination of the guideline. The guideline group members did not receive payments. N.P. declared grants from Bayer Pharma (research and consultancy) and NIHR-research POISE; consulting fees from Abbott, Astellas, Bayer, Besins, Lawley, Mithra, Theramex, Viatris; honoraria from Astellas, Bayer, Besins, Gedeon Richter, Theramex, Viatris; support for attending meetings and/or travel from Astellas, Bayer, Theramex, Viatris; President, International Menopause Society, Medical Advisory Committee member, British Menopause Society, Patron Daisy Network. A.J.V. declared grants from Amgen Australia, Australian NHMRC, and Australian MRFF; consulting fees from IQ Fertility; honoraria from the Australasian Menopause Society; participation on a Data Safety Monitoring Board or Advisory Board of Astellas; Board Member of the International Menopause Society (2020 to current) and Past president of the Australasian Menopause Society (2017-2019); R.A.A. declared grants from Roche (Research support, to institution), and participation on a Data Safety Monitoring Board of Bayer. M.C. declared grants from NHI; payments or honoraria from Up-to-Date (as editor/reviewer); Board Member of American Society of Reproductive Medicine, and of American Gynecological and Obstetrical Society. M.D. declared (NIHR-HTA NIHR133461; NIHR128757; Action GN2818) consulting fees from a small personal medical practice, support for attending meetings and/or travel from ESHRE, Bayer and UCLH special Trustees; Participation on the Advisory Board of the British Menopause Society, UKSTORE project, the Progress Educational Trust, and the Turner Syndrome Support Society UK; Leadership or fiduciary roles in the British Fertility Society (Trustee), Elizabeth Garrett Anderson Hospital Charity (chair of Trustees), and the Essex Wynter charitable trust (Trustee). C.E. declared being Chair of a SIG from the Royal Australian College of General Practitioners Integrative Medicine Specific Interest Group and Program Lead for Next Practice Western Sydney Integrative Health. C.H.G. declared grants from Novo Nordisk Foundation (Nos. NNF15OC0016474 and NNF20OC0060610), sygesikringen danmark (No 2022-0189), and the Independent Research Fund Denmark (Nos. 0134-00406 and 0134-00130B); consulting fees from Novo Nordisk, Merck, and Astra Zeneca. S.K. declared grants from Roche diagnostics. A.K. declared grants from NIH R01 5R01HD101475; consulting fees as Medical Reviewer for Flo and for Healthline; honoraria as Medical Consultant for Summus; support for attending meetings from the Reproductive Scientist Development Program; Society for Reproductive Investigation Council Member and Society for Assisted Reproduction Registry/Validation Chair; R.E.N. declared consulting fees from Astellas, Bayer Pharma, Besins Healthcare, Fidia, Theramex; honoraria from Abbott, Astellas, Exeltis, Fidia, Gedeon Richter, Merck & Co, Novo Nordisk, Shionogi Limited, Theramex, Viatris; payment for expert testimony from Vichy Laboratories; Participation in Data Safety Monitoring Board of Advisory board from Astellas and Bayer Healthcare; President elect of the International Menopause Society (IMS). H.T. declared a grant from NHMRC Centre for Research Excellence for women's health in reproductive life. A.B. declared being chair of the Daisy Network Charity. The other authors have no conflicts of interest to declare.DisclaimerThis guideline represents the views of ESHRE, ASRM, CRE-WHiRL, and IMS, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. The collaborating societies make no warranty, expressed or implied, regarding the clinical practice guidelines and specifically exclude any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.).

Evidence-based guideline: premature ovarian insufficiency(†)(‡)

Panay N et al., 2024·Climacteric

How should premature/primary ovarian insufficiency (POI) be diagnosed and managed, based on the best available evidence from published literature? The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae and treatment of POI. POI presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life, on fertility and on bone, cardiovascular and cognitive health. Although hormone therapy (HT) can mitigate some of these effects, many questions still remain regarding the optimal management of POI. STUDY DESIGN, SIZE, The guideline was developed according to the structured methodology for development of European Society of Human Reproduction and Embryology (ESHRE) guidelines. Key questions were determined by a group of experts and informed by a scoping survey of women and healthcare professionals. Literature searches and assessment were then performed. Papers published up to 30 January 2024 and written in English were included in the guideline. An integrity review was conducted for the randomized controlled trials on POI included in the guideline. PARTICIPANTS/MATERIALS, SETTING, Based on the collected evidence, recommendations were formulated and discussed within the guideline development group until consensus was reached. Women with lived experience of POI informed the recommendations in general, and particularly those on provision of care. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline development group and the ESHRE Executive Committee. MAIN New data indicate a higher prevalence of POI, 3.5%, than was previously thought. This guideline aims to help healthcare professionals apply best practice care for women with POI. The recent update of the POI guideline covers 40 clinical questions on diagnosis of the condition, the different sequelae, including bone, cardiovascular, neurological and sexual function, fertility and general well-being, and treatment options, including HT. The list of clinical questions was expanded from the previous iteration of the guideline (2015) based on the scoping survey and appreciation of emerging knowledge of POI. Questions were added on the role of anti-Müllerian hormone (AMH) in the diagnosis of POI, fertility preservation, muscle health and specific considerations for HT in iatrogenic POI. Additionally, the topic on complementary treatments was extended with specific focus on non-hormonal treatments and lifestyle management options. Significant changes from the previous 2015 guideline include the recommendations that only one elevated follicle stimulating hormone (FSH) >25 IU is required for diagnosis of POI and guidance that AMH testing, repeat FSH measurement and/or AMH may be required where there is diagnostic uncertainty. Recommendations were also updated regarding genetic testing, estrogen doses and regimens, use of the combined oral contraceptive and testosterone therapy. Women with lived experience of POI informed the recommendations on provision of care. LIMITATIONS, The guideline describes different management options, but it must be acknowledged that for most of these options, supporting evidence is limited for POI. The guideline provides healthcare professionals with clear advice on best practice in POI care, based on the best evidence currently available. In addition, a list of research recommendations is provided to guide further studies in POI.

Ischemic Stroke in Users of Combined Hormonal Contraceptives: A Danish Registry Study

Letnar G et al., 2024·Stroke

The combined hormonal contraceptive (CHC) with ethinylestradiol and progestins is the most widely used contraceptive method among young women and is used by millions worldwide. However, uncertainties exist about the risk of ischemic stroke associated with the use of CHCs with low-dose ethinylestradiol (<50-µg ethinylestradiol) and with the newest fourth-generation progestins that have only been sparsely investigated for the risk of ischemic stroke. In this cohort study based on Danish registries covering the entire Danish female population aged 18 to 49 years from 2004 to 2021, we investigated incidence rate ratios (IRRs) of ischemic stroke using CHCs compared with nonuse of hormonal contraceptives. Analyses focused on comparing CHCs based on ethinylestradiol content (30-40versus ≤20-μg ethinylestradiol), progestin generation (second, third, and fourth) in CHCs, and route of administration (monophasic versus sequential). Poisson regression models adjusting for age, education, ethnicity, calendar year, and medication used for risk factors were utilized. In total, 1 711 757 nonpregnant women contributed 14 697 788 person-years to the investigation. For users of CHCs containing <50-µg ethinylestradiol, the adjusted IRR was increased by 1.77 (95% CI, 1.62-1.93) compared with nonusers of hormonal contraceptives. IRR did not differ between CHCs with 30to 40and ≤20-µg ethinylestradiol. Adjusted incidence rate difference between CHC users and nonusers of hormonal contraceptives ranged from 1 in 100 000 women per year in 18 to 24 years of age to 24 in 100 000 women per year in ≥45 years of age. Incidence rate in users of fourth-generation CHCs was 30% lower than that of second-generation CHCs adjusted IRR (0.70 [95% CI, 0.50-0.98]). IRR for users of third-generation CHCs did not differ significantly from that of second-generation users adjusted IRR (1.14 [95% CI, 0.97-1.35]). Use of CHCs was associated with a 1.77 higher IRR of ischemic stroke. IRR did not relate to ethinylestradiol content in users of CHCs with <50-µg ethinylestradiol. IRR was 30% lower in users of fourth-generation than in users of second-generation CHCs.

Using anti-Müllerian hormone to predict premature ovarian insufficiency: a retrospective cross-sectional study

Huang Y et al., 2024·Front Endocrinol (Lausanne)

Premature ovarian insufficiency/failure (POI/POF) is a significant issue for women of reproductive age. Anti-Müllerian hormone (AMH) is a potential biomarker of ovarian reserve, but its clinical value in diagnosing and predicting POI/POF remains unclear. This study aimed to analyze the correlation between AMH and basal follicle-stimulating hormone (FSH) levels in women aged 18 to 40 and evaluate AMH's predictive value for POI/POF. A total of 21,143 participants aged 18-40 who visited the gynecology department or underwent physical examinations at the International Peace Maternity and Child Health Hospital in Shanghai, China, from July 2016 to June 2021 were enrolled. Demographic information and laboratory test results were collected, including age, FSH, AMH, E2 and test dates. Participants were grouped by FSH and AMH levels, and subgroup analyses were performed to investigate the relationship between these hormones and age. The AMH level associated with POI risk was evaluated using restricted cubic splines (RCS) and logistic regression. Clinical benefit was assessed by decision curve analysis (DCA). Participants with higher FSH levels had significantly lower median AMH levels and vice versa(p<0.001). At AMH ≥ 0.5 ng/mL, FSH levels were normal or slightly elevated with age. At AMH level below 0.5ng/ml,basal FSH increased significantly with age. At FSH <10 IU/L, AMH levels show a trend of rising and then decreasing with age, reaching a peak at approximately 25 years old and gradually decreasing with age. At FSH ≥10 IU/L, AMH levels show a gradual downward trend with age, and at FSH >40 IU/L, AMH levels remain very low to undetectable values. The RCS showed that the risk of POI/POF in the overall population sharply increased until serum AMH reached a low level (below 0.5ng/ml). DCA showed that a low AMH level had good clinical diagnostic utility in predicting POI/POF. Our analysis of a large dataset suggests that serum AMH levels are inversely correlated with FSH levels and that AMH is a good predictor of POI until it drops to a low level.

RTAC Code of Practice for Reproductive Technology Units (Australia and New Zealand) - December 2024 (Issue 9)

Reproductive Technology Accreditation Committee et al., 2024·Fertility Society of Australia and New Zealand - RTAC

RTAC Code of Practice (Issue 9) governing accreditation requirements for reproductive technology units operating in Australia and New Zealand. Sets standards for clinical, laboratory, and quality-management practices that ART centres must meet to remain RTAC-accredited and eligible to submit cycles to ANZARD. Includes patient safety, embryology laboratory, donor-program, and incident-reporting requirements. Effective from December 2024.

Recognizing Endometrial Cancer Risks in Perimenopausal and Postmenopausal Experiences: Insights From Community Qualitative Interviews and Workshop

Ibrahim M et al., 2024·J Obstet Gynaecol Can

To evaluate the experiences of perimenopausal and postmenopausal women in British Columbia, their perceptions of expected reproductive aging, and potential concerns about endometrial cancer (EC). We interviewed 31 midlife community women of diverse backgrounds and hosted a workshop for more in-depth discussion. We summarized relayed experiences and beliefs through a thematic and descriptive analysis of participant stories and workshop feedback. Participants demonstrated a somewhat simplistic understanding of midlife changes, facing this phase of life with a "tough-it-out" attitude rather than seeking medical help for arising symptoms. Awareness of EC and EC-specific risk factors, such as obesity, was low. Confusion between cervical and EC was common. Although abnormal bleeding was seen as potentially of concern, many opted to wait before seeking medical help. Workshop participants stressed the need to include awareness about EC in a broader conversation about perimenopause and menopause and suggested strategies for disseminating EC awareness. Community women in British Columbia demonstrated low awareness of EC-associated symptoms and risk factors. There is little information to help distinguish when perimenopausal abnormal uterine bleeding is of concern and when to seek help. This highlights the need to enhance knowledge of EC and its risk factors in perimenopause among the public and among health care providers.

Family Formations in Fertility Treatment 2022

Human Fertilisation and Embryology Authority, 2024

# Family formations in fertility treatment 2022 Preliminary UK family type statistics for IVF and DI treatment, storage, November 2024 [Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/zpjlvhnd/family-formations-in-fertility-treatment-2022-underlying-dataset.xlsx "Download the underlying dataset for the ‘Family formations in fertility treatment 2022’ report") ## - [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#main-points) - [Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#introduction) - [Section 1: The proportion of female same-sex couples and single patients having fertility treatment has changed](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-1) - [Section 2: IVF birth rates highest among female same-sex couples](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-2) - [Section 3: Single patients are starting IVF younger than previous years](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-3) - [Section 4: Patient population changes between those storing eggs and thawing them](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-4) - [Section 5: Average IVF multiple birth rate decreased across all family types](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-5) - [Section 6: Female same-sex couples and single patients had the lowest levels of NHS funding](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-6) - [Section 7: Up to two-thirds o...

Is Vaginal Repair a Good Option for Severe Cesarean Scar Defect? Comparison of Women With or Without Residual Myometrium

Bardet L et al., 2024·J Minim Invasive Gynecol

To compare outcomes of vaginal surgery in women with moderate or severe symptomatic cesarean scar defect (with or without residual myometrium). Retrospective cohort study. Gynecology department of a teaching hospital. Fifty-three women, between January 2014 and December 2019, underwent vaginal surgery for symptomatic 20 women with moderate defect (with residual myometrium) and 33 with severe defect (without residual myometrium). Vaginal surgical approach to repair cesarean scar defect. MAIN surgery by comparing the myometrial residual thickness before and after surgery. The secondary objectives were evaluation of vaginal surgery efficacy on symptoms resolution, per and postoperative courses, and subsequent fertility. Failure rate was evaluated as the need for a second surgery. After vaginal surgery, the residual myometrium significantly increased from 2.4 mm ± 0.9 mm to 6.6 mm ± 2.4 mm (p <.01) in the moderate group and from 0 mm to 4.4 mm ± 2.2 mm (p <.01) in the severe group. The prevalence of abnormal uterine bleeding was significantly reduced after surgery in both groups (p <.01). Pelvic pain was significantly reduced only in the moderate group (p <.01). The rate of complications (5% vs 9.1%) and second surgery (15% vs 24.2%) were not significantly different between moderate and severe groups, respectively. The median time to conceive (7 months vs 12 months); pregnancy rates (84.6% vs 68.2%); and live birth rates (76.9% vs 50%) were not statistically significant in the moderate and severe groups respectively, with 90% of pregnancies occurring naturally. Women delivered by cesarean section at 38 weeks of gestation in both groups, and no uterine rupture was reported. Despite the absence of residual myometrium, vaginal repair of severe cesarean scar defect was effective in increasing myometrial thickness, in relieving bleeding symptoms, and in allowing to achieve pregnancy.

Case Series: Diagnosis and Treatment of Four Rare Cancers by a Single Surgeon Due to Systematic Mapping and Near Contact Techniques

Whittaker NM, AAGL 2024·J Minim Invasive Gynecol

No standard criteria exist for how to perform a diagnostic laparoscopy. This case series provides evidence of the importance of standardized, reproducible techniques. A single non-oncologic gynecologic surgeon used Near-Contact Laparoscopy (NCL) and Systematic Mapping of the Abdomen and Pelvis (S-MAP) techniques, resulting in the incidental finding and curative treatment of 4 rare cancers over 3 years. Three were neuroendocrine tumors of the appendix (incidence 0.95/100,000; probability of 3 0.0000000001). The fourth was a 2 mm well-differentiated papillary mesothelioma (WDPM). All 4 were cured. 3 of 3 infertile patients subsequently achieved pregnancy. The NCL technique was originally coined by Dr. Redwine (PMID: 3190209). The S-MAP method was described in the NaProTechnology textbook by Dr. Thomas Hilgers, and the S-MAP term coined by this author. Case D used robotic-assisted laser excision. Standardization should be incorporated as the gold standard.

Additives in Processed Foods as a Potential Source of Endocrine-Disrupting Chemicals: A Review

Paramasivam A et al., 2024·Journal of xenobiotics

Processed foods, accounting for most consumable food categories today, contain considerable amounts of food additives. Food additives are substances added to food products to improve taste, consistency, appearance, or shelf life. Various food additives, such as phthalates, bisphenol A, tartrazine, erythrosine, artificial sweeteners, and parabens, have been identified as potential sources of endocrine-disrupting chemicals (EDCs) in processed foods. EDCs are substances that frequently interfere with the regular functioning of the endocrine system, creating an unusual environment in the biological system, which leads to adverse health effects such as the disruption of hormone synthesis, receptor binding, and signal transduction pathways, as well as energy metabolic homeostatic disorders which potentially increasing the risk of obesity, type-2 diabetes, cardiometabolic diseases and may also trigger allergic reactions. Consequently, they can also impact mammary gland development, and reproductive function, further leading to developmental abnormalities. This review aims to insights into the various food additives that act as potential endocrine-disrupting chemicals (EDCs) and to describe their applications in the food industry, as well as the failure of hormonal homeostatic mechanisms, which eventually result in hazardous health effects. It also outlines strategies to reduce the use of food additives and suggests alternative additives with minimal or no endocrine-disrupting properties, highlighting their importance for maintaining human health.

Ovarian reserve does not influence natural conception: insights from infertile women

Galati G et al., 2024·Archives of gynecology and obstetrics

There is several albeit not univocal evidence suggesting that ovarian reserve is not related to the chance of natural pregnancy, provided that the remnant follicular pool is sufficient to ensure regular menstrual cycles. Nevertheless, available studies have some methodological limitations, and the issue cannot be considered definitively ascertained. To further address this issue, we retrospectively selected infertile women whose infertility diagnostic work-up was unremarkable (unexplained infertility-cases) and matched them by age and study period to a group of infertile women who were diagnosed with severe male infertility (controls). If ovarian reserve impacts on natural fertility, one had to expect lower ovarian reserve among women with unexplained infertility. Tested biomarkers included AMH, AFC and day 2-3 serum FSH. The primary aim was the frequency of women with serum AMH < 0.7 ng/ml. Two-hundred fifty-two women with unexplained infertility and 252 women with male infertility were included. All biomarkers of ovarian reserve did not differ between the study groups. AMH levels < 0.7 ng/mL were observed in 26 (10%) women with unexplained infertility and 35 (14%) women with male infertility (p = 0.28). The adjusted OR was 0.76 (95% CI: 0.44-1.33). Significant differences did not also emerge when repeating this dichotomous analysis using other biomarkers and other thresholds for the definition of low-ovarian reserve. This study confirms that ovarian reserve is unremarkable to natural conception. Physicians and patients should be aware of this concept to avoid inappropriate counseling and undue clinical decisions.

State of the Fertility Sector 2023/2024

Human Fertilisation and Embryology Authority, 2024

# State of the fertility sector 2023/24 Annual publication (1st April 2023 – 31st March 2024) 1st October 2024 [Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/cjwjns5j/state-of-the-fertility-sector-2023-2024-underlying-dataset.xlsx "State of the fertility sector 2023-2024 - underlying dataset") ## - [How we regulate](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#how-we-regulate) - [1\. Inspections in 2023/24](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-1) - [2\. There were 226 non-compliances identified at inspection in 2023/24](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-2) - [3\. In 2023/24, 135 clinics were licensed by the HFEA to provide fertility treatment, storage and/or research](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-3) - [4\. Total incidents reduced by 8% compared to the previous financial year](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-4) - [5\. Fewer Ovarian hyperstimulation syndrome (OHSS) incidents were reported in 2023/24](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-5) - [6\. Patient complaints in 2023/24 were consistent with the previous financial year](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#section-6) - [About our data](https://www.hfea.gov.uk/about-us/publications/research-and-data/state-of-the-fertility-sector-2023-2024/#about-our-data) ## The Human Fertilisation and Embryology Authority (HFEA) is the independent regulator of fertility treatment and human embryo research in the United Ki...

Increased Incidence of Endometriosis Coexisting with Polycystic Ovary Syndrome in Infertile Patients

Mukherjee T et al., 2024

Prospective 1-year assessment of within-woman variability of follicular and luteal phase lengths in healthy women prescreened to have normal menstrual cycle and luteal phase lengths

Henry S et al., 2024·Hum Reprod

What is the relative length variance of the luteal phase compared to the follicular phase within healthy, non-smoking, normal-weight, proven normally ovulatory, premenopausal women with normal-length menstrual cycles? Prospective 1-year data from 53 premenopausal women with two proven normal-length (21-36 days) and normally ovulatory (≥10 days luteal) menstrual cycles upon enrollment showed that, despite 29% of all cycles having incident ovulatory disturbances, within-woman follicular phase length variances were significantly greater than luteal phase length variances. Many studies report menstrual cycle variability, yet few describe variability in follicular and luteal phase lengths. Luteal lengths are assumed 'fixed' at 13-14 days. Most studies have described follicular and luteal phase variability between-women. STUDY DESIGN, SIZE, This study was a prospective, 1-year, observational cohort study of relative follicular and luteal phase variability both between and within community-dwelling women with two documented normal-length (21-36 days) and normally ovulatory (≥10 days luteal phase) menstrual cycles prior to enrollment. Eighty-one women enrolled in the study and 66 women completed the 1-year study. This study analyzed data from 53 women with complete data for ≥8 cycles (mean 13). PARTICIPANTS/MATERIALS, SETTING, Participants were healthy, non-smoking, of normal BMI, ages 21-41 with two documented normal-length (21-36 days) and normally ovulatory (≥10 days luteal phase) menstrual cycles prior to enrollment. Participants recorded first morning temperature, exercise durations, and menstrual cycle/life experiences daily in the Menstrual Cycle Diary. We analyzed 694 cycles utilizing a twice-validated least-squares Quantitative Basal Temperature method to determine follicular and luteal phase lengths. Statistical analysis compared relative follicular and luteal phase variance in ovulatory cycles both between-women and within-woman. Normal-length cycles with short luteal phases or anovulation were considered to have subclinical ovulatory disturbances (SOD). Main The 1-year overall 53-woman, 676 ovulatory cycle variances for menstrual cycle, follicular, and luteal phase lengths were 10.3, 11.2, and 4.3 days, respectively. Median variances within-woman for cycle, follicular, and luteal lengths were 3.1, 5.2, and 3.0 days, respectively. Menstrual cycles were largely of normal lengths (98%) with 55% of women experienced >1 short luteal phase (<10 days) and 17% experienced at least one anovulatory cycle. Within-woman follicular phase length variances were greater than luteal phase length variances (P < 0.001). However, follicular (P = 0.008) and luteal phase length (P = 0.001) variances, without differences in cycle lengths, were greater in women experiencing any anovulatory cycles (n = 8) than in women with entirely normally ovulatory cycles (n = 6). LIMITATIONS, Limitations of this study include the relatively small cohort, that most women were White, initially had a normal BMI, and the original cohort required two normal-length and normally ovulatory menstrual cycles before enrollment. Thus, this cohort's data underestimated population menstrual cycle phase variances and the prevalence of SOD. Our results reinforce previous findings that the follicular phase is more variable than the luteal phase in premenopausal women with normal-length and ovulatory menstrual cycles. However, our study adds to the growing body of evidence that the luteal phase is not predictably 13-14 days long. STUDY FUNDING/COMPETING INTEREST(S): This medical education project of the University of British Columbia was funded by donations to the Centre for Menstrual Cycle and Ovulation Research. The authors do not have any conflicts of interest to disclose. N/A.

Nonlinear correlation between serum vitamin D levels and the incidence of endometrial polyps in infertile women

Zhou R et al., 2024·Hum Reprod

Are serum vitamin D levels associated with the incidence of endometrial polyps (EPs) in infertile patients? Serum 25(OH)D levels were nonlinearly correlated with the incidence of EPs in infertile women. EPs are a common condition that may affect the receptivity of the endometrium in women of reproductive age. Vitamin D regulates cell proliferation and differentiation, apoptosis, angiogenesis, anti-inflammation, and immunomodulation, in addition to its well-known functions in balancing calcium and phosphorus. Previous studies have shown that vitamin D concentrations are associated with reproductive outcomes, and that low vitamin D levels are associated with the incidence of colorectal polyps and nasal polyps. There is little evidence regarding the relationship between EPs and serum vitamin D levels. STUDY DESIGN, SIZE, We conducted a cross-sectional study using data from Guangdong Women and Children Hospital from January 2019 to October 2023, enrolling 3107 patients. PARTICIPANTS/MATERIALS, SETTING, A total of 3107 infertile patients who underwent hysteroscopy were included in this study; 642 patients had endometrial polyps and 2465 had a normal uterine cavity. Hysteroscopy findings included risk of EPs, polyp size, percentage of multiple polyps, and incidence of chronic endometritis (CE). Serum vitamin D were assessed by measuring total 25(OH)D using chemiluminescence. According to international guideline recommendations for vitamin D deficiency, patients the <50 nmol/l group and the ≥50 nmol/l group. Univariable and multivariable logistic regression models, stratified analyses, and smooth curve fitting were used to examine the relationship between serum 25(OH)D levels and risk of EPs. MAIN Of all patients, 23.8% (740/3107) were vitamin D deficient (<50 nmol/l). The incidence of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group (24.9% vs 19.3%; P = 0.001). However, there were no differences in polyp size, proportion of multiple polyps, and presence of CE between the two groups. After controlling for confounders, 25(OH)D ≥ 50 nmol/l (compared with <50 nmol/l) was negatively associated with risk of EPs (adjusted OR, 0.733; 95% CI, 0.598-0.898). Other variables that had an impact on polyp incidence included BMI, type of infertility, CA125, and CD138-positive plasma cells. In addition, a linear regression model between age and serum 25(OH)D levels showed a positive linear association. Subgroup analyses were performed for different age groups, and the risk of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group, both in the younger subgroup (23.8% vs 19.1%) and in the older subgroup (28.0% vs 19.9%). The smooth curve fitting model showed a nonlinear correlation between 25(OH)D levels and risk of EPs (nonlinear P-value = 0.020), with an optimal threshold of 51.8 nmol/l for 25(OH)D levels. Moreover, subgroup smooth curve fitting models showed a nonlinear correlation between 25(OH)D levels and polyp risk in patients aged <35 years (nonlinear P-value = 0.010), whereas a linear correlation between 25(OH)D levels and polyp risk was found in patients aged ≥35 years (nonlinear P-value = 0.682). LIMITATIONS, Caution should be exercised in interpreting our findings as this is a correlational study and causality cannot be inferred from our results. In addition, because of strict inclusion and exclusion criteria, our results may not be generalizable to unselected populations, including premenopausal women or women of other races. This study demonstrated for the first time that vitamin D deficiency is an independent risk factor for the incidence of EPs in infertile patients. Identifying modifiable risk factors (e.g. vitamin D deficiency) can help in the development of new strategies for treating polyps or to protect against polyp development. Further clinical intervention trials and laboratory studies are needed to evaluate the effect of vitamin D on the development of EPs and to elucidate the mechanisms. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the National Natural Science Foundation of China (82101718) and Natural Science Foundation of Guangdong Province, China (2022A1515010776). No competing interest was involved in this study. N/A.

Maternal periconception hyperglycemia, preconception diabetes, and risk of major congenital malformations in offspring

Rotem RS et al., 2024·Hum Reprod

What are the roles of maternal preconception diabetes and related periconceptional hyperglycemia on the risk of major congenital malformations (MCMs) in offspring? Maternal periconceptional glycated hemoglobin (HbA1c) levels over 5.6% were associated with an increased risk of congenital heart defects (CHD) in the offspring, and maternal preconception diabetes was associated with an increased risk of CHD, including when HbA1c levels were within euglycemic ranges. Maternal preconception diabetes has been linked with MCMs in the offspring. However, evidence concerning associations with specific periconception serum measures of hyperglycemia, and susceptibility of different organ systems, is inconsistent. Moreover, limited evidence exists concerning the effectiveness of antidiabetic medications in mitigating diabetes-related teratogenic risks. STUDY DESIGN, SIZE, A large Israeli birth cohort of 46 534 children born in 2001-2020. PARTICIPANTS/MATERIALS, SETTING, Maternal HbA1c test results were obtained from 90 days before conception to mid-pregnancy. Maternal diabetes, other cardiometabolic conditions, and MCMs in newborns were ascertained based on clinical diagnoses, medication dispensing records, and laboratory test results using previously validated algorithms. Associations were modeled using generalized additive logistic regression models with thin plate penalized splines. MAIN Maternal periconceptional HbA1c value was associated with CHD in newborns, with the risk starting to increase at HbA1c values exceeding 5.6%. The association between HbA1c and CHD was stronger among mothers with type 2 diabetes mellitus (T2DM) compared to the other diabetes groups. Maternal pre-existing T2DM was associated with CHD even after accounting for HbA1C levels and other cardiometabolic comorbidities (odds ratio (OR)=1.89, 95% CI 1.18, 3.03); and the OR was materially unchanged when only mothers with pre-existing T2DM who had high adherence to antidiabetic medications and normal HbA1c levels were considered. LIMITATIONS, The rarity of some specific malformation groups limited the ability to conduct more granular analyses. The use of HbA1c as a time-aggregated measure of glycemic control may miss transient glycemic dysregulation that could be clinically meaningful for teratogenic risks. The observed association between pre-existing diabetes and the risk of malformations within HbA1c levels suggests underlying causal pathways that are partly independent of maternal glucose control. Therefore, treatments for hyperglycemia might not completely mitigate the teratogenic risk associated with maternal preconception diabetes. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by NIH grants K99ES035433, R01HD097778, and P30ES000002. None of the authors reports competing interests. N/A.

Endometriosis and pregnancy outcomes - another piece to a complex puzzle

Farland LV et al., 2024·Fertil Steril

HFEA Code of Practice (9th edition, version 9.4)

Human Fertilisation and Embryology Authority, 2024

The HFEA Code of Practice gives guidance to clinics about the proper conduct of activities licensed under the Human Fertilisation and Embryology Act 1990 (as amended). The 9th edition (effective 26 October 2023) was further amended for version 9.4 (effective 1 October 2024). The Code consolidates statutory regulations, license conditions, clinic governance, staff training and qualifications, identity checks and consent, gamete and embryo storage, donor recruitment and screening, donation arrangements, treatment licensing, pre-implantation genetic testing, multiple births policy, surrogacy, witnessing procedures, traceability, adverse incidents reporting, complaints, research licensing, and information disclosure. Compliance with the Code is a statutory requirement for all UK clinics licensed by the HFEA. Version 9.4 includes updated guidance on donor compensation (effective October 2024) and known donation for people with undetectable HIV (effective November 2024).

The fate of hazardous textile pollutants in an upcycling process for post-consumer garments

Åström T et al., 2024·Cleaner Engineering and Technology

Association of mixed exposure to microplastics with sperm dysfunction: a multi-site study in China

Zhang C et al., 2024·EBioMedicine

Microplastics are environmental pollutants detected in various human organs and tissues. These particles originate from multiple sources including the degradation of larger plastic items and the intentional inclusion in consumer goods. Potential risks for human health resulting from microplastics exposure have also been reported. However, the distribution in the male reproductive system and its effect remains largely unknown. This study aims to investigate the presence of multiple microplastics in human semen and urine and their association with sperm quality in a multi-site study across China. We conducted a cross-sectional study involving 113 male participants from three regions in China. Semen and urine samples were collected and analysed using Raman microscopy to detect polystyrene (PS), polypropylene (PP), polycarbonate (PC), polyethylene (PE), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), and acrylonitrile butadiene styrene (ABS). Semen quality parameters, including total sperm count, concentration, motility, and morphology, were assessed. Statistical analyses, including single and multi-variable models, were used to evaluate the relationship between microplastic exposure and semen quality, with a focus on PTFE, after adjusting confounding factors of age, body mass index (BMI), smoking, alcohol drinking, and sites. Microplastics were detected in all semen and urine samples, with participants typically exposed to 3-5 different types. The detection rates of PS, PP and PE were the highest. Notably, PTFE exposure was significantly associated with decreased semen quality. Participants exposed to PTFE showed reductions in total sperm count [188.90 ± 163.71 vs. 207.67 ± 132.36 million, p = 0.091], sperm concentration [52.13 ± 47.47 vs. 58.32 ± 37.26 million/mL, p = 0.041], and progressive motility [40.29% ± 19.06 vs. 34.11% ± 17.02, p = 0.083]. The multi-linear regression analysis indicated that each additional type of microplastic exposure was associated with a significant decrease in total sperm number [β = -15.4 (95% CI: -25.6, -5.2)], sperm concentration [β = -7.2 (95% CI: -12.4, -2.0)], and progressive motility [β = -8.3 (95% CI: -13.5, -3.1)]. Latent category analysis further refined these groups by types of microplastic exposure, highlighting specific types more strongly associated with decreased semen quality (OR = 3.5, 95% CI: 1.8, 6.9, p < 0.001). The nomogram can be used to assess the risk of sperm damage by combining the type of microplastic exposure in urine with age and BMI. Our findings highlight the potential reproductive health risks posed by microplastic contamination, particularly PTFE, a non-stick pan coating material, and raise concerns about the potential of urine testing as an indicator of male reproductive microplastic exposure. Future research is warranted to further elucidate the mechanisms underlying the adverse effects of microplastics on male fertility and cross-generational effects. This study was funded by the Clinical Research Project of Shanghai Municipal Commission of Health and Family planning (20224Y0085), Open Fund Project of Guangdong Academy of Medical Sciences (YKY-KF202202), CAMS Innovation Fund for Medical Sciences (2019-I2M-5-064), Shanghai Clinical Research Center for Gynecological Diseases (22MC1940200), Shanghai Urogenital System Diseases Research Centre (2022ZZ01012), Key Discipline Construction Project (2023-2025) of Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai (GWVI-11.1-35, GWVI-11.2-YQ29) and Shanghai Frontiers Science Research Base of Reproduction and Development.

The Long-term Rate of Repeat Surgery After Optimal Excision Surgery of Endometriosis at a Single Tertiary Referral Center

Yeung P et al., 2025·Acta Scientific Women's Health

The primary purpose of this prospective cohort study was to determine if treating endometriosis with optimal excision surgery leads to lower rates of repeat surgery as compared to historical rates of repeat surgery by ablation. A secondary outcome was to examine whether the use of hormonal suppression differed before surgery, depending on the stage of endometriosis found at surgery. Optimal excision was defined as completely excising all areas of abnormal peritoneum, wherever found in the pelvis, having looked systematically with near contact laparoscopy. All surgeries were performed by a single surgeon specializing in optimal excision at a tertiary referral center. The rate of repeat surgery after optimal excision surgery for endometriosis was remarkably low (2.5%, 15/620) as compared to historical rates of repeat surgery by ablation. Additionally, the lack of significant evidence between hormonal suppression use and progression of stage of endometriosis provides implicit evidence that hormonal suppression does not prevent progression of the disease. Further controlled studies are needed to verify these findings.

Supplementation with Folic Acid or 5-Methyltetrahydrofolate and Prevention of Neural Tube Defects: An Evidence-Based Narrative Review

Samaniego-Vaesken ML et al., 2024·Nutrients

Folic acid (FA), which in its chemical form is pteroylglutamic acid, is the fully oxidised, water-soluble, monoglutamic form of vitamin B9. This compound is part of the folate group but with higher bioavailability, and it is found in vitamin supplements and fortified foods and drugs. Folate metabolism is complex and associated with various metabolic pathways, all of which confer protection on the cell and allow its survival. We conducted a non-systematic search of articles published in English and Spanish including controlled trials, cohort studies, systematic re-views, and meta-analyses were included, as well as key studies in animal models related to pharmacokinetic studies. "folic acid", "folates", "5-metyltetrahydrofolate", "5-MTHF", "neural tube defects", "supplementation", "fortification", AND "homocysteine" A crucial role demonstrated for FA is to help prevent neural tube defects (NTDs). However, more studies are definitely still needed to establish 5-MTHF as a safe and effective therapeutic approach comparable with FA. Moreover, there is a lack of clinical studies that evaluate the efficacy of 5-MTHF supplementation in the prevention of NTDs. The present evidence-based narrative review discusses differences between FA and 5-MTHF in terms of structure, metabolism, bioavailability, clinical efficacy, and safety. Despite the potential value of 5-MTHF as an alternative to FA, clinical studies would be urgently needed to support the efficacy, dosage, timing, and/or safety of its use as a supplement.

Neuroactive hormones and personal growth: associations in Chilean adolescents (ages 12-25) with ovulatory dysfunction

Del Río JP et al., 2024·Front Psychol

Hormones produced by the hypothalamic-pituitary-adrenal-gonadal (HPAG) axis are crucial for modulating central nervous system (CNS) function and development throughout a person's life. Disruptions in HPAG function can impact psychological development, particularly during adolescence-a period marked by psychological growth and the maturation of the HPAG axis. An early indicator of HPAG alterations is ovulatory dysfunction (OD), a common condition among adolescents. This study explored the associations between neuroactive hormones and personal growth in adolescents with OD. Female participants aged 12-25 years with OD were recruited, and assessments were conducted to profile their basic hormonal levels and various dimensions of individual development, including self-concept clarity, sense of coherence, self-esteem, perfectionism, self-control, and mood states. Adolescents with OD (n = 117) had lower self-concept clarity and self-esteem compared to reference data. A significant portion of the sample displayed elevated levels of tension (71.25%), confusion (62.5%), fatigue (58.22%), and depression (52.6%). Self-esteem scores were negatively correlated with DHEAS (r = -0.224; p = 0.026) and glucose (r = -0.249; p = 0.010). Higher levels of free testosterone were associated with increased depression scores (coef = 0.2398; p = 0.002), whereas higher estradiol levels were linked to lower aggressiveness scores (coef = -0.0648; p = 0.001). These findings indicate that hormonal imbalances in adolescents with OD could affect personal growth. Further research is needed to establish causal relationships between the variables considered.

Health risks from exposure to chemicals in clothing - Non-regulated halogenated aromatic compounds

Carlsson J et al., 2024·Chemosphere

The objective of the present study was to investigate some commonly detected halogenated textile pollutants for their bioavailability and hazardous properties. Release into artificial sweat and skin absorption in vitro were examined as well as mutagenic effects by Ames test, and skin-sensitizing properties from a peptide reactivity assay combined with a cell test. All investigated compounds were shown to migrate from the textile into sweat and be absorbed by the skin, although to a different extent. The experimental values for migration were found to be up to 390 times higher compared to literature values. Two of the studied compounds, 2,5-dinitrochlorobenzene and 3,5-dinitrobromobenzene, both exhibited mutagenic effects in the Ames test, while both 2,5-dinitrochlorobenzene and 2,6-dichlorobenzene-1,4-diamine were classified as skin sensitizers. The allergenic reactivity of the latter was found to be due to an oxidized transformation product. Risks for the induction of skin allergy and other non-carcinogenic effects from dermal exposure to the individual compounds were found low, even when considering clothing with the highest reported levels. However, the complex mixtures of chemicals often present in garments may still constitute a health risk, especially when considering the many hours of daily exposure. It is important to further study the toxicity of other frequently occurring chemicals as well as the synergistic effects of chemicals that co-occur in clothing.

Associations of Early Prolonged Secondary Amenorrhea in Women With and Without HIV

Swann SA et al., 2024·Open Forum Infect Dis

The menstrual cycle is a critical indicator of women's health. Early prolonged secondary amenorrhea increases risks for morbidity and mortality. Menstrual cycle research in women with HIV is inconsistent and often lacks an adequate comparison sample. We aimed to determine whether women with HIV have a higher lifetime prevalence of amenorrhea and whether this is independently associated with HIV and/or other biopsychosocial variables. With data from 2 established HIV cohorts, participants assigned female at birth were eligible if aged ≥16 years, not pregnant/lactating, and without anorexia/bulimia nervosa history. Amenorrhea was defined by self-reported history of (1) no menstrual flow for ≥12 months postmenarche not due to pregnancy/lactation, medications, or surgery or (2) early menopause or premature ovarian insufficiency. Multivariable logistic regression models explored biopsychosocial covariates of amenorrhea. Overall, 317 women with HIV (median age, 47.5 years [IQR, 39.2-56.4]) and 420 women without HIV (46.2 [32.6-57.2]) were included. Lifetime amenorrhea was significantly more prevalent among women with HIV than women without HIV (24.0% vs 13.3%). In the multivariable analysis, independent covariates of amenorrhea included HIV (adjusted odds ratio, 1.70 [95% CI, 1.10-2.64]), older age (1.01 [1.00-1.04]), White ethnicity (1.92 [1.24-3.03]), substance use history (6.41 [3.75-11.1]), and current food insecurity (2.03 [1.13-3.61]). Nearly one-quarter of women with HIV have experienced amenorrhea, and this is associated with modifiable risk factors, including substance use and food insecurity. Care providers should regularly assess women's menstrual health and advocate for actionable sociostructural change to mitigate risks.

Prenatal Cannabis Use and Maternal Pregnancy Outcomes

Young-Wolff KC et al., 2024·JAMA internal medicine

Many studies have evaluated whether in utero cannabis exposure is associated with fetal and neonatal outcomes, yet little is known about whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. To evaluate whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. DESIGN, SETTING, This population-based retrospective cohort study included pregnancies in Northern California from January 2011 to December 2019 that lasted 20 weeks or longer and were screened for prenatal cannabis use. Prenatal cannabis use was defined as any self-reported use during early pregnancy or a positive toxicology test result based on universal screening at entrance to prenatal care (approximately 8-10 weeks' gestation). Self-reported frequency of use (daily, weekly, monthly or less, never, unknown), use defined only by self-report, and use defined only by toxicology test results were examined. Electronic health record data were used to gestational hypertension, preeclampsia, eclampsia, gestational diabetes, gestational weight gain greater and less than guidelines, placenta previa, placental abruption, placenta accreta, and severe maternal morbidity. Adjusted risk ratios (aRRs) were calculated using a modified Poisson regression. The sample (n = 316 722 pregnancies; 250 221 unique individuals) included 84 039 (26.5%) Asian/Pacific Islander, 20 053 (6.3%) Black, 83 145 (26.3%) Hispanic, and 118 333 (37.4%) White individuals; the mean (SD) age was 30.6 (5.4) years. Overall, 20 053 (6.3%) screened positive for prenatal cannabis use; 2.9% were positive by self-report, 5.3% by toxicology testing, and 1.8% by both. The frequency of cannabis use was 1930 (0.6%) daily, 2345 (0.7%) weekly, 4892 (1.5%) monthly or less, and 10 886 (3.4%) unknown. Prenatal cannabis use was associated with greater risk of gestational hypertension (aRR, 1.17; 95% CI, 1.13-1.21), preeclampsia (aRR, 1.08; 95% CI, 1.01-1.15), weight gain less than (aRR, 1.05; 95% CI, 1.01-1.08) and greater than (aRR, 1.09; 95% CI, 1.08-1.10) guidelines, and placental abruption (aRR, 1.19; 95% CI, 1.05-1.36). The pattern of results was similar when defining prenatal cannabis use only by self-report or only by toxicology testing, and associations between the frequency of prenatal cannabis use and outcomes varied with outcome. The results of this cohort study suggest that prenatal cannabis use was associated with several adverse maternal health outcomes during pregnancy. Continued research is needed to understand whether characteristics of prenatal cannabis use (eg, dose, mode, and timing) moderate these associations.

A nomogram and risk stratification to predict subsequent pregnancy loss in patients with recurrent pregnancy loss

Li M et al., 2024·Hum Reprod

Could the risk of subsequent pregnancy loss be predicted based on the risk factors of recurrent pregnancy loss (RPL) patients? A nomogram, constructed from independent risk factors identified through multivariate logistic regression, serves as a reliable tool for predicting the likelihood of subsequent pregnancy loss in RPL patients. Approximately 1-3% of fertile couples experience RPL, with over half lacking a clear etiological factor. Assessing the subsequent pregnancy loss rate in RPL patients and identifying high-risk groups for early intervention is essential for pregnancy counseling. Previous prediction models have mainly focused on unexplained RPL, incorporating baseline characteristics such as age and the number of previous pregnancy losses, with limited inclusion of laboratory and ultrasound indicators. STUDY DESIGN, SIZE, The retrospective study involved 3387 RPL patients who initially sought treatment at the Reproductive Immunology Clinic of Renji Hospital, Shanghai Jiao Tong University School of Medicine, between 1 January 2020 and 31 December 2022. Of these, 1153 RPL patients met the inclusion criteria and were included in the analysis. PARTICIPANTS/MATERIALS, SETTING, RPL was defined as two or more pregnancy losses (including biochemical pregnancy loss) with the same partner before 28 weeks of gestation. Data encompassing basic demographics, laboratory indicators (autoantibodies, peripheral immunity coagulation, and endocrine factors), uterine and endometrial ultrasound results, and subsequent pregnancy outcomes were collected from enrolled patients through initial questionnaires, post-pregnancy visits fortnightly, medical data retrieval, and telephone follow-up for lost patients. R software was utilized for data cleaning, dividing the data into a training cohort (n = 808) and a validation cohort (n = 345) in a 7:3 ratio according to pregnancy success and pregnancy loss. Independent predictors were identified through multivariate logistic regression. A nomogram was developed, evaluated by 10-fold cross-validation, and compared with the model incorporating solely age and the number of previous pregnancy losses. The constructed nomogram was evaluated using the AUC, calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA). Patients were then categorized into lowand high-risk subgroups. MAIN We included age, number of previous pregnancy losses, lupus anticoagulant, anticardiolipin IgM, anti-phosphatidylserine/prothrombin complex IgM, anti-double-stranded DNA antibody, arachidonic acid-induced platelet aggregation, thrombin time and the sum of bilateral uterine artery systolic/diastolic ratios in the nomogram. The AUCs of the nomogram were 0.808 (95% CI: 0.770-0.846) in the training cohort and 0.731 (95% CI: 0.660-0.802) in the validation cohort, respectively. The 10-fold cross-validated AUC ranged from 0.714 to 0.925, with a mean AUC of 0.795 (95% CI: 0.750-0.839). The AUC of the nomogram was superior compared to the model incorporating solely age and the number of previous pregnancy losses. Calibration curves, DCAs, and CICAs showed good concordance and clinical applicability. Significant differences in pregnancy loss rates were observed between the lowand high-risk groups (P < 0.001). LIMITATIONS, This study was retrospective and focused on patients from a single reproductive immunology clinic, lacking external validation data. The potential impact of embryonic chromosomal abnormalities on pregnancy loss could not be excluded, and the administration of medication to all cases impacted the investigation of risk factors for pregnancy loss and the model's predictive efficacy. This study signifies a pioneering effort in developing and validating a risk prediction nomogram for subsequent pregnancy loss in RPL patients to effectively stratify their risk. We have integrated the nomogram into an online web tool for clinical applications. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Natural Science Foundation of China (82071725). All authors have no competing interests to declare. N/A.

Endometriosis Typology and Ovarian Cancer Risk

Barnard ME et al., 2024·JAMA

Endometriosis has been associated with an increased risk of ovarian cancer; however, the associations between endometriosis subtypes and ovarian cancer histotypes have not been well-described. To evaluate the associations of endometriosis subtypes with incidence of ovarian cancer, both overall and by histotype. DESIGN, SETTING, Population-based cohort study using data from the Utah Population Database. The cohort was assembled by matching 78 893 women with endometriosis in a 1:5 ratio to women without endometriosis. Endometriosis cases were identified via electronic health records and categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other. Estimated adjusted hazard ratios (aHRs), adjusted risk differences (aRDs) per 10 000 women, and 95% CIs for overall ovarian cancer, type I ovarian cancer, and type II ovarian cancer comparing women with each type of endometriosis with women without endometriosis. Models accounted for sociodemographic factors, reproductive history, and past gynecologic operations. In this Utah-based cohort, the mean (SD) age at first endometriosis diagnosis was 36 (10) years. There were 597 women with ovarian cancer. Ovarian cancer risk was higher among women with endometriosis compared with women without endometriosis (aHR, 4.20 [95% CI, 3.59-4.91]; aRD, 9.90 [95% CI, 7.22-12.57]), and risk of type I ovarian cancer was especially high (aHR, 7.48 [95% CI, 5.80-9.65]; aRD, 7.53 [95% CI, 5.46-9.61]). Ovarian cancer risk was highest in women with deep infiltrating endometriosis and/or ovarian endometriomas for all ovarian cancers (aHR, 9.66 [95% CI, 7.77-12.00]; aRD, 26.71 [95% CI, 20.01-33.41]), type I ovarian cancer (aHR, 18.96 [95% CI, 13.78-26.08]; aRD, 19.57 [95% CI, 13.80-25.35]), and type II ovarian cancer (aHR, 3.72 [95% CI, 2.31-5.98]; aRD, 2.42 [95% CI, -0.01 to 4.85]). Ovarian cancer risk was markedly increased among women with ovarian endometriomas and/or deep infiltrating endometriosis. This population may benefit from counseling regarding ovarian cancer risk and prevention and could be an important population for targeted screening and prevention studies.

The association between the use of fertility indicators and fecundability in a Danish preconception cohort

Pedersen ES et al., 2024·Paediatr Perinat Epidemiol

The use of fertility indicators to predict ovulation has largely been studied for contraceptive purposes, while less so as fertility-promoting tools. To investigate the association between fertility indicators and fecundability in Danish women trying to conceive. Web-based preconception cohort study. We analysed data from 11,328 females aged 18-49 years trying to conceive without fertility treatment for ≤6 menstrual cycles, from the Danish SnartGravid.dk and SnartForældre.dk cohorts (2007-2023). Participants reported the use of fertility indicators (counting days since the last menstrual period, cervical fluid monitoring, urinary ovulation testing, feeling ovulation, using a smartphone fertility app and measuring basal body temperature [BBT]). Time to pregnancy was measured in menstrual cycles ascertained by self-reported pregnancy status. We estimated fecundability ratios (FR) and 95% confidence intervals (CI) using proportional probabilities regression models adjusted for age, socio-economic position, health indicators, reproductive history and gynaecological factors. Fertility indicators were used by 63.3% of participants at study entry. Counting days was the most common (46.9%), while measuring BBT was the least (3.0%). Other indicators ranged from 17.0% to 23.6%, with 69.7% using more than one indicator. Compared with non-use, use of any fertility indicator was associated with greater fecundability (adjusted FR 1.14, 95% CI 1.08, 1.19). Cervical fluid monitoring showed the strongest association (aFR 1.46, 95% CI 1.03, 2.07), followed by urinary ovulation testing (aFR 1.35, 95% CI 1.16, 1.58) and counting days (aFR 1.18, 95% CI 1.09, 1.29). Feeling ovulation and fertility apps were modestly associated with fecundability, while measuring BBT was not associated. Sensitivity analysis restricting to ≤2 cycles of attempt time and two cycles of follow-up showed an aFR for any indicator use of 1.21 (95% CI 1.13, 1.31). In this Danish preconception cohort, use of fertility indicators was associated with a higher fecundability, varying by type of indicator.

Evaluating Pregnancy Rates in Fertility Awareness-Based Methods for Family Planning: Simulated Comparison of Correct Use to Avoid, Method-Related, and Total Pregnancy Rates

Stanford JB et al., 2024·Linacre Q

Fertility awareness-based methods (FABMs), also known as natural family planning (NFP), enable couples to identify the days of the menstrual cycle when intercourse may result in pregnancy ("fertile days"), and to avoid intercourse on fertile days if they wish to avoid pregnancy. Thus, these methods are fully dependent on user behavior for effectiveness to avoid pregnancy. For couples and clinicians considering the use of an FABM, one important metric to consider is the highest expected effectiveness (lowest possible pregnancy rate) during the correct use of the method to avoid pregnancy. To assess this, most studies of FABMs have reported a method-related pregnancy rate (a cumulative proportion), which is calculated based on all cycles (or months) in the study. In contrast, the correct use to avoid pregnancy rate (also a cumulative proportion) has the denominator of cycles with the correct use of the FABM to avoid pregnancy. The relationship between these measures has not been evaluated quantitatively. We conducted a series of simulations demonstrating that the method-related pregnancy rate is artificially decreased in direct proportion to the proportion of cycles with intermediate use (any use other than correct use to avoid or targeted use to conceive), which also increases the total pregnancy rate. Thus, as the total pregnancy rate rises (related to intermediate use), the method-related pregnancy rate falls artificially while the correct use pregnancy rate remains constant. For practical application, we propose the core elements needed to assess correct use cycles in FABM studies. Fertility awareness-based methods (FABMs) can be used by couples to avoid pregnancy, by avoiding intercourse on fertile days. Users want to know what the highest effectiveness (lowest pregnancy rate) would be if they use an FABM correctly and consistently to avoid pregnancy. In this simulation study, we (1) the method-related pregnancy rate; and (2) the correct use pregnancy rate. We show that the method-related pregnancy rate is biased too low if some users in the study are not using the method consistently to avoid pregnancy, while the correct use pregnancy rate obtains an accurate estimate. In FABM studies, the method-related pregnancy rate is biased too low, but the correct use pregnancy rate is unbiased.

Menstrual Cramps in Anovulatory versus Normally Ovulatory Cycles - SARS-COV-2 Pandemic Daily Data Plus a Meta-Analysis of Cramps and Anovulation

Mann G et al., 2024·J Pain Res

It is asserted that primary dysmenorrhea/menstrual cramps only occur in ovulatory menstrual cycles. Our first objective was to present detailed menstrual cramps information in normally ovulatory versus anovulatory cycles from a single-cycle cohort study during the SARS-CoV-2 Pandemic. Secondly, we reviewed the literature for cohort studies documenting both menstrual cramps and ovulation. The Menstruation and Ovulation Study 2 recruited 108 women ages 19-35 years to a prospective, observational single-cycle study, recording cramps daily (0-4 scale) in the Menstrual Cycle Diary© and assessing normal ovulation (luteal length ≥10 days) by the validated Quantitative Basal Temperature© (Mean Temperature Method). We searched databases for « primary dysmenorrhea » / » menstrual cramps »; « menstrual cycles »; « anovulation », finding four valid publications. In 75 women/cycles during the Pandemic, mean age was 28.5, body mass index 23.5, and higher education (16 years); 40 normally ovulatory and 35 anovulatory cycles had similar lengths (29.5-30.0 days), respectively (P=0.571). However, anovulatory cycles recorded significantly worse menstrual cramps versus normally ovulatory cycles; anovulatory median intensity was 1.9 versus 1.6, and Cramp Score was 8 versus 6 in normally ovulatory cycles (P=0.017). Four publications in 273 women (991 cycles) showed cramps in both anovulatory and ovulatory cycles; three were in adolescent/young adult women, one of which documented a significantly greater percentage of cramps in ovulatory cycles. The 694 cycles in premenopausal women (20-41 years) showed similar percentages of symptomatic cramps in cycles of both ovulatory types. Meta-analysis documented significantly higher cramp prevalence in ovulatory cycles (OR 2.10; 95% CI 1.31, 3.37; P=0.002). This is the first documentation of more intense and frequent cramps in anovulatory cycles. However, meta-analysis showing the presence of symptomatic cramps in both ovulatory and anovulatory cycles documented they were twice as prevalent in ovulatory menstrual cycles. “Worse Menstrual Cramps in Anovulatory Cycles”. Medicine has long believed that menstrual cramps only occur in ovulatory menstrual cycles that release an egg and have high progesterone levels that decrease before the next period. The notion was that dropping progesterone levels triggered release of prostaglandins that cause the pain and uterus muscle contractions of menstrual cramps. This research studied 75 community women aged 19–35 years for a single cycle during COVID-19. Forty women had normally ovulatory cycles and 35 had anovulatory cycles with a similar mean cycle length of 29.7 days. Women in both groups were similar in age, weight, education and other reproductive characteristics. Women recorded Menstrual Cycle Diary© daily experiences for cramp presence and intensity (scored 0–4). Ovulation was documented by daily first morning temperatures analyzed by the valid Quantitative Basal Temperature© method. Results showed menstrual cramps occurred in both normally ovulatory and anovulatory cycles. Surprisingly, anovulatory compared with ovulatory cycles had cramps that lasted longer (4 rather than 3 days), were more intense (1.9 versus 1.6) and with significantly higher Cramp Scores (of 8 versus 6). We also found four other published studies showing cramps occurred in both anovulatory and ovulatory cycles. A meta-analysis of these, however, showed that cramps were twice as frequent in ovulatory cycles. These results matter because they stimulate the search for more accurate understandings of why menstrual cramps occur. They will likely stimulate more effective therapies for the rare, intense menstrual cramps that currently are not effectively treated by anti-inflammatory medicines such as ibuprofen.

Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model

Xu Q et al., 2024·Brain, behavior, and immunity

Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.

Overview of indigo biosynthesis by Flavin-containing Monooxygenases: History, industrialization challenges, and strategies

Fan C et al., 2024·Biotechnology Advances

Indigo is a natural dye extensively used in the global textile industry. However, the conventional synthesis of indigo using toxic compounds like aniline, formaldehyde, and hydrogen cyanide has led to environmental pollution and health risks for workers. This method also faces growing economic, sustainability, and environmental challenges. To address these issues, the concept of bio-indigo or indigo biosynthesis has been proposed as an alternative to aniline-based indigo synthesis. Among various enzymes, Flavin-containing Monooxygenases (FMOs) have shown promise in achieving a high yield of bio-indigo. However, the industrialization of indigo biosynthesis still encounters several challenges. This review focuses on the historical development of indigo biosynthesis mediated by FMOs. It highlights several factors that have hindered industrialization, including the use of unsuitable chassis (Escherichia coli), the toxicity of indole, the high cost of the substrate L-tryptophan, the water-insolubility of the product indigo, the requirement of reducing reagents such as sodium dithionite, and the relatively low yield and high cost compared to chemical synthesis. Additionally, this paper summarizes various strategies to enhance the yield of indigo synthesized by FMOs, including redundant sequence deletion, semi-rational design, cheap precursor research, NADPH regeneration, large-scale fermentation, and enhancement of water solubility of indigo.

Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry

Dernoncourt A et al., 2024·Hum Reprod

What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester? In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages. Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL. STUDY DESIGN, SIZE, The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals. PARTICIPANTS/MATERIALS, SETTING, Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth. MAIN One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01). LIMITATIONS, Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered. Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system. STUDY FUNDING/COMPETING INTEREST(S): The research received no specific funding, and the authors declare no competing interests. clinicaltrial.gov NCT05557201.

Comparison of laparoscopic and hysteroscopic surgical treatments for isthmocele: A prospective cohort

Hosseini R et al., 2024·Turkish journal of obstetrics and gynecology

To evaluate the clinical outcomes of laparoscopic and hysteroscopic surgical approaches for treating symptomatic isthmocele and identify their associated factors. Forty-six patients with symptomatic isthmocele diagnosed using transvaginal saline infusion sonohysterography were enrolled in this prospective cohort study. Patients underwent either laparoscopic or hysteroscopic isthmoplasty based on their residual myometrial thicknesses and fertility desires and were subsequently followed by clinical and ultrasonographic examinations. Twenty-two patients underwent laparoscopy and 24 underwent hysteroscopic surgery. At baseline, there was no significant difference in the mean age and years since the last cesarean section between the two groups. However, the hysteroscopy group had a higher mean parity and previous cesarean sections (p=0.00, 0.03). The most common symptoms were abnormal uterine bleeding, infertility, and dysmenorrhea. The mean baseline residual myometrial thickness was significantly higher in the laparoscopy group (p=0.00), and only laparoscopic surgery led to a significant increase in residual myometrial thickness in patients (p=0.00). Both procedures significantly reduced abnormal uterine bleeding (p=0.00), but only laparoscopy reduced infertility (p=0.00) and hysteroscopy reduced dysmenorrhea (p=0.03). Hysteroscopy showed better symptom resolution in younger patients (p=0.01), whereas age did not affect laparoscopy outcomes. Both approaches showed similar effectiveness in resolving abnormal uterine bleeding, with laparoscopy excelling in infertility resolution and hysteroscopy excelling in dysmenorrhea resolution. AMAÇ: Bu çalışmanın amacı semptomatik istmosel tedavisinde laparoskopik ve histeroskopik cerrahi yaklaşımların klinik sonuçlarını değerlendirmek ve ilişkili faktörleri belirlemektir. GEREÇ VE YÖNTEMLER: Bu prospektif kohort çalışmasına transvajinal salin infüzyon sonohisterografi kullanılarak semptomatik istmosel tanısı konan 46 hasta dahil edildi. Hastalara rezidüel miyometrial kalınlık ve doğurganlık isteklerine göre laparoskopik veya histeroskopik istmoplasti uygulandı ve ardından hastalar klinik ve ultrasonografik muayenelerle takip edildi. Yirmi iki hastaya laparoskopi, yirmi dört hastaya ise histeroskopik cerrahi uygulandı. Başlangıçta, iki grup arasında ortalama yaş ve son sezaryenden bu yana geçen yıllar açısından anlamlı bir fark yoktu. Ancak histeroskopi grubunda ortalama parite ve önceki sezaryenlerin sayısı daha yüksekti (p=0,00, 0,03). En sık görülen semptomlar anormal uterin kanama, kısırlık ve dismenore idi. Başlangıçtaki ortalama rezidüel miyometrial kalınlık laparoskopi grubunda anlamlı derecede yüksekti (p=0,00) ve yalnızca laparoskopik cerrahi hastalarda anlamlı rezidüel miyometrial kalınlık artışına yol açtı (p=0,00). Her iki prosedür de anormal uterin kanamayı önemli ölçüde azalttı (p=0,00), ancak yalnızca laparoskopi kısırlığı azalttı (p=0,00) ve histeroskopi dismenoreyi azalttı (p=0,03). Histeroskopi genç hastalarda semptomlarda daha fazla düzelme sağladı (p=0,01), yaş ise laparoskopi sonuçlarını etkilemedi. SONUÇ: Her iki yaklaşım da anormal uterin kanamanın çözümünde benzer etkinlik göstermiştir; laparoskopi kısırlığın çözümünde ve histeroskopi dismenorenin çözümünde üstündür.

Fertility Treatment 2022: Preliminary Trends and Figures

Human Fertilisation and Embryology Authority, 2024

# Fertility treatment 2022: Preliminary UK statistics for IVF and DI treatment, storage, July 2024 [Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/5jfpm1cw/fertility-treatment-2022-preliminary-trends-and-figures-underlying-dataset.xlsx "Fertility treatment 2022: preliminary trends and figures - underlying dataset") ## - [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#main-points) - [Note on preliminary data](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#note-on-preliminary-data) - [Section 1: Average IVF pregnancy rate using fresh embryo transfers increased](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#section-1) - [Section 2: Average IVF pregnancy and birth rates using frozen embryo transfers similar to previous years](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#section-2) - [Section 3: Average age at first IVF treatment increased above 35 years of age for first time](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#section-3) - [Section 4: New egg and sperm donors increased by 21% from 2019 to 2022](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#section-4) - [Section 5: Egg storage fastest growing treatment, but accounted for 5% of all cycles in 2022](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2022-preliminary-trends-and-figures/#section-5) - [Section 6: Multiple births from IVF at lowest UK average yet of 4%](https://www.hfea.gov.uk/about-us/publications/research-and-data/fe...