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Editorial: Immunocellular mechanisms and endocrine organs

Gallo D et al., 2023·Front Endocrinol (Lausanne)

EDITORIAL article Front. Endocrinol., 16 May 2023Sec. Cellular Endocrinology Volume 14 - 2023 | //doi.org/10.3389/fendo.2023.1214230

Application of systematic evidence mapping to identify available data on the potential human health hazards of selected market-relevant azo dyes

Keshava C et al., 2023·Environment International

Azo dyes are used in textiles and leather clothing. Human exposure can occur from wearing textiles containing azo dyes. Since the body's enzymes and microbiome can cleave azo dyes, potentially resulting in mutagenic or carcinogenic metabolites, there is also an indirect health concern on the parent compounds. While several hazardous azo dyes are banned, many more are still in use that have not been evaluated systematically for potential health concerns. This systematic evidence map (SEM) aims to compile and categorize the available toxicological evidence on the potential human health risks of a set of 30 market-relevant azo dyes. Peer-reviewed and gray literature was searched and over 20,000 studies were identified. These were filtered using Sciome Workbench for Interactive computer-Facilitated Text-mining (SWIFT) Review software with evidence stream tags (human, animal, in vitro) yielding 12,800 unique records. SWIFT Active (a machine-learning software) further facilitated title/abstract screening. DistillerSR software was used for additional title/abstract, full-text screening, and data extraction.Results187 studies were identified that met populations, exposures, comparators, and outcomes (PECO) criteria. From this pool, 54 human, 78 animal, and 61 genotoxicity studies were extracted into a literature inventory. Toxicological evidence was abundant for three azo dyes (also used as food additives) and sparse for five of the remaining 27 compounds. Complementary search in ECHA's REACH database for summaries of unpublished study reports revealed evidence for all 30 dyes. The question arose of how this information can be fed into an SEM process. Proper identification of prioritized dyes from various databases (including U.S. EPA's CompTox Chemicals Dashboard) turned out to be a challenge. Evidence compiled by this SEM project can be evaluated for subsequent use in problem formulation efforts to inform potential regulatory needs and prepare for a more efficient and targeted evaluation in the future for human health assessments.

Bone health and prevalent fractures in women with polycystic ovary syndrome: a meta-analysis and endocrine-context pathophysiology review

Prior JC et al., 2023·Expert Rev Endocrinol Metab

Bone health in those with Polycystic Ovary Syndrome (PCOS) is complex, but the general consensus is that cortical areal bone mineral density (aBMD) sites will be higher in PCOS than in ageand BMI-similar controls. However, spine aBMD sites may be lower, especially in non-obese PCOS. Whether or not incident fracture risk is increased in PCOS is currently controversial; no meta-analysis has yet assessed prevalent fractures. We assessed the bone effects of PCOS-related ovarian hormone alterations, e.g. androgen excess, tonically normal/higher estradiol, and lower-than-normal progesterone levels. We also highlighted evidence that common PCOS medications (e.g. combined hormonal contraceptives [CHC], metformin, and spironolactone) have important bone effects. In adolescents, meta-analysis of CHC showed significant negative aBMD changes. Inflammation has negative PCOS bone effects and is linked with CHC use. Is fracture risk altered by PCOS? Our meta-analysis showed a 25% increased risk of prevalent fracture in PCOS versus controls; this did not reach statistical significance. Future prospective research needs to collect and evaluate ovulation characteristics, progesterone exposure, and adolescent CHC use, in addition to the complex variables that may influence risks for prevalent or incident fragility fractures and/or for cortical and cancellous aBMD values in PCOS.

Menstrual cycle length variation by demographic characteristics from the Apple Women's Health Study

Li H et al., 2023·NPJ digital medicine

Menstrual characteristics are important signs of women's health. Here we examine the variation of menstrual cycle length by age, ethnicity, and body weight using 165,668 cycles from 12,608 participants in the US using mobile menstrual tracking apps. After adjusting for all covariates, mean menstrual cycle length is shorter with older age across all age groups until age 50 and then became longer for those age 50 and older. Menstrual cycles are on average 1.6 (95%CI: 1.2, 2.0) days longer for Asian and 0.7 (95%CI: 0.4, 1.0) days longer for Hispanic participants compared to white non-Hispanic participants. Participants with BMI ≥ 40 kg/m2 have 1.5 (95%CI: 1.2, 1.8) days longer cycles compared to those with BMI between 18.5 and 25 kg/m2. Cycle variability is the lowest among participants aged 35-39 but are considerably higher by 46% (95%CI: 43%, 48%) and 45% (95%CI: 41%, 49%) among those aged under 20 and between 45-49. Cycle variability increase by 200% (95%CI: 191%, 210%) among those aged above 50 compared to those in the 35-39 age group. Compared to white participants, those who are Asian and Hispanic have larger cycle variability. Participants with obesity also have higher cycle variability. Here we confirm previous observations of changes in menstrual cycle pattern with age across reproductive life span and report new evidence on the differences of menstrual variation by ethnicity and obesity status. Future studies should explore the underlying determinants of the variation in menstrual characteristics.

Combined hormonal contraceptive use is not protective against musculoskeletal conditions or injuries: a systematic review with data from 5 million females

White L et al., 2023·Br J Sports Med

Assess the association between combined hormonal contraceptives (CHC) use and musculoskeletal tissue pathophysiology, injuries or conditions. Systematic review with semiquantitative analyses and certainty of evidence assessment, guided by the Grading of Recommendations Assessment, Development and Evaluation approach. MEDLINE, EMBASE, CENTRAL, SPORTDiscus, CINAHL searched from inception to April 2022. Intervention and cohort studies that assessed the association between new or ongoing use of CHC and an outcome of musculoskeletal tissue pathophysiology, injury or condition in postpubertal premenopausal females. Across 50 included studies, we assessed the effect of CHC use on 30 unique musculoskeletal outcomes (75% bone related). Serious risk of bias was judged present in 82% of studies, with 52% adequately adjusting for confounding. Meta-analyses were not possible due to poor outcome reporting, and heterogeneity in estimate statistics and comparison conditions. Based on semiquantitative synthesis, there is low certainty evidence that CHC use was associated with elevated future fracture risk (risk ratio 1.02-1.20) and total knee arthroplasty (risk ratio 1.00-1.36). There is very low certainty evidence of unclear relationships between CHC use and a wide range of bone turnover and bone health outcomes. Evidence about the effect of CHC use on musculoskeletal tissues beyond bone, and the influence of CHC use in adolescence versus adulthood, is limited. Given a paucity of high certainty evidence that CHC use is protective against musculoskeletal pathophysiology, injury or conditions, it is premature and inappropriate to advocate, or prescribe CHC for these purposes. This review was registered on PROSPERO CRD42021224582 on 8 January 2021.

GnRH agonists in the treatment of symptomatic endometriosis: a review

Surrey ES, 2023·F S Rep

The development of highly potent gonadotropin-releasing hormone agonists (GnRHa) allowed for a significant addition to options for the medical management of symptomatic endometriosis. Pituitary GnRH receptor down-regulation leads to a hypogonadotropic and secondary hypoestrogenic state resulting in lesion regression and symptom improvement. There may be an additional effect of these agents on the inflammatory processes associated with endometriosis as well. This is a review of critical milestones in the clinical application of these agents. Most initial trials of various GnRHa employed danazol as a control and demonstrated general equivalence in reducing symptoms and extent of lesions but without hyperandrogenic side effects and adverse metabolic changes induced by the latter. Short-acting GnRHa is administered intranasally or subcutaneously. Longer-acting preparations are administered intramuscularly or as subcutaneous implants. GnRHa also decrease symptom recurrence rates after surgical management. The hypoestrogenic side effects, including bone mineral density loss and vasomotor symptoms, have limited the duration of use of these agents alone to six months. The use of an appropriate add-back allows for the mitigation of side effects while maintaining efficacy and allowing extension of use for up to 12 months. There is a limited amount of data regarding the use of GnRHa in adolescents out of concern for the effect on developing bone. These agents should be used with caution in this group. The lack of dose flexibility, need for parental administration, and side effect profiles represent drawbacks to GnRHa use. The development of oral GnRH antagonists with short half-lives, variable dosing, and decreased side effects represents an exciting alternative.

Evaluation of a fertility awareness-based shared decision-making tool part 1: Study design and impact on clinician knowledge

Duane M et al., 2023·PEC Innov

To assess the impact of a Shared Decision-Making (SDM) tool for fertility awareness-based methods (FABMs) of family planning. Clinicians familiar with at least one FABM were randomly invited to participate in a prospective cross-over study to compare usual practice to the use of the SDM tool when discussing FABMs with patients. Patients completed surveys preand post-office visit and six months later. The primary outcome explored the effect of online education on use of the SDM tool on clinicians' knowledge of FABMs. Of 278 clinicians contacted, 54% could not be reached, and 15% did not provide women's health services. The 26 clinicians enrolled were experienced, with more than half recommending FABMs for ≥10 years, and 73% recommending more than one FABM to patients. Knowledge scores significantly improved after online training and use of the SDM tool (baseline mean score = 9.54 (scale of 0-12); post-training mean score = 10.73, p < 0.002). Education about FABMs and training on use of the SDM tool improved knowledge scores even among an experienced cohort of clinicians. The novel SDM tool can better equip clinicians to meet the rising patient interest in FABMs.

Validation of a Brief Measure for Complicated Grief Specific to Reproductive Loss

Buskmiller C et al., 2023·Cureus

Objective Complicated grief reactions follow some pregnancy outcomes, like miscarriage, stillbirth, neonatal death, infant death, selective reduction, or termination of pregnancy. Stigma can delay treatment and worsen outcomes. Screening tools such as the Edinburgh Postnatal Depression Scale detect complicated grief poorly, and specific tools for prolonged or complicated grief after a reproductive loss are cumbersome. In this study, a five-item questionnaire to detect complicated grief after reproductive loss of any type was designed and preliminary validated. Methods A questionnaire patterned after the extensively validated Brief Grief Questionnaire (BGQ) was created by a group of physicians and lay advocates to employ non-traumatic but specific language related to grief after miscarriage, stillbirth, neonatal death, infant death, selective reduction, or termination of pregnancy. One hundred and forty women at a large academic center were recruited in person and via social media to validate the questionnaire with well-studied instruments for anxiety (7-item Panic Disorder Severity Scale, PDSS), trauma (22-item Impact of Events Scale), and reproductive grief and depressive symptoms (33-item Perinatal Grief Scale [PGS]). Results The response rate was 74.9%. Of the 140 participants, 18 (12.8%) experienced their loss during high-risk pregnancies, and 65 (46.4%) were recruited via social media. Seventy-one (51%) respondents had a score > 4, a positive screen for the BGQ. On average, women experienced their loss 2 years prior to participation (IQR 1-5 years). Cronbach's alpha was 0.77 (95% CI: 0.69-0.83). The goodness of fit indices of the model met Fornell and Larker criteria (RMSEA = 0.167, CFI = 0.89, SRMR = 0.06). The AVE was 0.42 and the CR 0.78. Conclusions This investigator-created screening tool is internally consistent and meets preliminary criteria for discriminant validity. This tool can be refined prior to testing for sensitivity and specificity in screening for complicated grief after a reproductive loss.

Efforts to transfer ectopic embryos to the uterine cavity: A systematic review

Thomas C et al., 2023·J Obstet Gynaecol Res

The objectives of this review are to identify and characterize attempts to transfer ectopic embryos to the uterus, and to understand arguments for and against the feasibility of such an intervention. An electronic literature search involved all English language articles published in MEDLINE (1948-), Web of Science (1899-), and Scopus (1960-) before July 1, 2022. Articles were included that identify or describe attempts to transfer the embryo from its ectopic location to the uterine cavity, or discuss the feasibility of such an intervention; there were no exclusion criteria (PROSPERO registration number CRD42022364913). The initial search yielded 3060 articles; 8 articles were included. Of these, two articles were case reports that described the successful transfer of the embryo from its ectopic location to the uterus, followed by term births; both cases involved laparotomy with salpingostomy, followed by transfer of the embryonic sac into the uterine cavity through an opening made in the uterine wall. The other six articles varied in type, and provided a number of arguments for and against the feasibility of such a procedure. The evidence and arguments identified in this review may help manage expectations for those interested in transferring an ectopically implanted embryo in the hope of continuing the pregnancy, but who are uncertain about the extent to which such a procedure has been attempted or may be possible. Isolated case reports, with no evidence of replication, should be interpreted with the utmost caution and do not constitute a procedure for clinical use.

The Influence of Gut Microbiota on Oxidative Stress and the Immune System

Kunst C et al., 2023·Biomedicines

The human gastrointestinal tract is home to a complex microbial community that plays an important role in the general well-being of the entire organism. The gut microbiota generates a variety of metabolites and thereby regulates many biological processes, such as the regulation of the immune system. In the gut, bacteria are in direct contact with the host. The major challenge here is to prevent unwanted inflammatory reactions on one hand and on the other hand to ensure that the immune system can be activated when pathogens invade. Here the REDOX equilibrium is of utmost importance. This REDOX equilibrium is controlled by the microbiota either directly or indirectly via bacterial-derived metabolites. A balanced microbiome sorts for a stable REDOX balance, whereas dysbiosis destabilizes this equilibrium. An imbalanced REDOX status directly affects the immune system by disrupting intracellular signaling and promoting inflammatory responses. Here we (i) focus on the most common reactive oxygen species (ROS) and (ii) define the transition from a balanced REDOX state to oxidative stress. Further, we (iii) describe the role of ROS in regulating the immune system and inflammatory responses. Thereafter, we (iv) examine the influence of microbiota on REDOX homeostasis and how shifts in proand anti-oxidative cellular conditions can suppress or promote immune responses or inflammation.

Physician Dispositions Toward Noninvasive Non-Hormonal Contraception

Davidson AV et al., 2023·Kans J Med

Evidence-based, nonbiased, counseling on contraceptive options, followed by shared decision-making, is key in facilitating reproductive justice in a diverse population. An estimated 3% of contraceptive users in the United States use fertility awareness-based methods (FABMs) for contraception, and demand for these methods is increasing. FABMs can be a highly effective form of family planning when used in accordance with evidence-based protocols. They are preferred by some patients due to medical contraindications to hormonal contraceptives, lack of side effects, religious convictions, preference to avoid hormones or contraceptive devices, improved body literacy, or a combination of the above. FABMs are infrequently covered in medical school curricula and are often perceived by physicians to be of low efficacy. There is an opportunity for improvement of physicians' evidence-based knowledge of FABMs, which has the potential to improve patient understanding of and access to the full menu of family planning options. A self-administered, cross-sectional survey was distributed to assess physician knowledge and opinions of FABMs by key university contacts. Univariate and bivariate statistics were calculated for close-ended questions and responses to open-ended questions were analyzed for common themes. A total of 79 participants completed the entire survey. Another 11 submitted partially completed surveys. For completed surveys, questions assessing knowledge of key concepts underlying FABMs, performance by specialty was 55% correct for OB/GYN (n = 16), 55% (n = 47) correct for family medicine, 36% (n = 10) correct for internal medicine, and 35% (n = 6) correct for pediatrics. Negative, neutral, mixed, and positive opinions related to FABMs were represented. There are opportunities to improve physicians' evidence-based knowledge of FABMs; this may improve patient-centered contraceptive care.

Effectiveness of a Postpartum Breastfeeding Protocol for Avoiding Pregnancy

Schneider MM et al., 2023·Linacre Q

The uses of cervical mucus and basal body temperature as indicators of return to fertility postpartum have resulted in high unintended pregnancy rates. In 2013, a study found that when women used urine hormone signs in a postpartum/breastfeeding protocol this resulted in fewer pregnancies. To improve the original protocol's effectiveness, (1) women were to increase the number of days tested with the Clearblue Fertility Monitor, (2) an optional second luteinizing hormone test could be done in the evening, and (3) instructions were given to manage the beginning of the fertile window for the first six cycles postpartum. The purpose of this study was to determine the correct and typical use effectiveness rates to avoid pregnancy in women who used a revised postpartum/breastfeeding protocol. A cohort review of an established data set from 207 postpartum breastfeeding women who used the protocol to avoid pregnancy was completed using Kaplan-Meier survival analysis. Total pregnancy rates that included correct and incorrect use pregnancies were eighteen per one hundred women over twelve cycles of use. For the pregnancies that met a priori criteria, the correct use pregnancy rates were two per one hundred over twelve months and twelve cycles of use and typical use rates were four per one hundred women at twelve cycles of use. The protocol had fewer unplanned pregnancies than the original, however, the cost of the method increased.

The Risk of Infertility After Surgery for Benign Ovarian Cysts

Shandley LM et al., 2023·Journal of women's health (2002)

There is a growing body of evidence that ovarian cystectomy may negatively impact ovarian reserve. However, it is unclear whether ovarian cyst surgery puts women at risk of future infertility. This study investigates whether surgery for benign ovarian cysts is associated with long-term infertility risk. Women aged 22-45 years (n = 1,537) were invited to participate in an interview about their reproductive histories, including whether they ever had infertility or ovarian cyst surgery. Each woman reporting cyst surgery was randomly matched to a comparison woman, who was assigned an artificial surgery age equal to that of her match. Matching was repeated 1,000 times. Adjusted Cox models were fit to examine time to infertility after surgery for each match. A subset of women was invited to participate in a clinic visit to assess markers of ovarian reserve (anti-Müllerian hormone [AMH], antral follicle count). Approximately 6.1% of women reported cyst surgery. Infertility after surgery was more common for women reporting cyst surgery than those without surgery after adjusting for age, race, body mass index, cancer history, parity before assigned surgery age, history of infertility before surgery age, and endometriosis (median-adjusted hazard ratio 2.41, 95% simulation interval 1.03-6.78). The estimated geometric mean (95% confidence interval [CI]) AMH levels of those who reported a history of ovarian cyst surgery were 1.08 (95% CI: 0.57-2.05) times those of women who reported no history of surgery. Those with a history of ovarian cyst surgery were more likely to report having a history of infertility compared with age-matched women who reported no history of cyst surgery. It is possible that both ovarian surgery to remove cysts and the conditions that lead women to develop cysts requiring surgery may affect subsequent successful conception.

Plastic used in in vitro fertilization procedures induces massive placental gene expression alterations

Kouakou F et al., 2023·EBioMedicine

The exposure to plastic derivatives during human life is deleterious. Infants conceived using ART (IVF or ICSI) have twice as many risks of major birth defects compared to naturally conceived infants. Could plastic ware used during ART trigger defects in the fetal development? Three groups of blastocysts were transferred to pseudopregnant mice. One was obtained after IVF and embryo development in plastic ware, the second in glass ware. The third, was obtained in vivo by natural mating. On day 16.5 of pregnancy, females were sacrificed and fetal organs collected for gene expression analysis. Fetal sex was determined by RT-PCR. RNA was extracted from a pool of five placental or brain samples coming from at least two litters from the same group and analyzed by hybridisation onto the mouse Affymetrix 430.2.0 GeneChips, confirmed by RT-qPCR for 22 genes. This study highlights a major impact of plastic ware on placental gene expression (1121 significantly deregulated genes), while glassware was much closer to in vivo offspring (only 200 significantly deregulated genes). Gene Ontology indicated that the modified placental genes were mostly involved in stress, inflammation and detoxification. A sex specific analysis revealed in addition a more drastic effect on female than male placentas. In the brains, whatever the comparison, less than 50 genes were found deregulated. Embryos incubated in plastic ware resulted in pregnancy with massive alterations of placental gene expression profile in concerted biological functions. There were no obvious effects on the brains. Besides other effects, this suggests that plastic ware in ART could be a cause of the increased level of pregnancy disorders observed recurrently in ART pregnancies. This study was funded by two grants from the Agence de la Biomedecine in 2017 and 2019.

Oral and Vaginal Hormonal Contraceptives Induce Similar Unfavorable Metabolic Effects in Women with PCOS: A Randomized Controlled Trial

Mosorin ME et al., 2023·J Clin Med

This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC, n = 13) or vaginal (CVC, n = 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased (p < 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC p < 0.001; CVC p = 0.007). OGTT glucose levels at 60 min (p = 0.011) and AUCglucose (p = 0.018) increased in the CVC group. Fasting insulin levels (p = 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC p = 0.004; CVC p = 0.042). There was a significant increase in triglyceride (p < 0.001) and hs-CRP (p = 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS.

Age at Natural Menopause in Women Living with HIV: A Cross-Sectional Study Comparing Self-Reported and Biochemical Data

Shayda A Swann et al., 2023·Viruses

Early menopause (<45 years) has significant impacts on bone, cardiovascular, and cognitive health. Several studies have suggested earlier menopause for women living with HIV; however, the current literature is limited by reliance on self-report data. We determined age at menopause in women living with HIV and socio-demographically similar HIV-negative women based on both self-report of menopause status (no menses for ≥12 months) and biochemical confirmation (defined as above plus follicle-stimulating hormone level ≥ 25 IU/mL). Multivariable median regression models assessed factors associated with menopause age, controlling for relevant confounders. Overall, 91 women living with HIV and 98 HIV-negative women were categorized as menopausal by self-report, compared to 83 and 92 by biochemical confirmation. Age at menopause did not differ significantly between groups, whether based on self-report (median [IQR]: 49.0 [45.3 to 53.0] vs. 50.0 [46.0 to 53.0] years; p = 0.28) or biochemical confirmation (50.0 [46.0 to 53.0] vs. 51.0 [46.0 to 53.0] years; p = 0.54). In the multivariable model, no HIV-related or psychosocial variables were associated with earlier age at menopause (all p > 0.05). Overall, HIV status per se was not statistically associated with an earlier age at menopause, emphasizing the importance of comparing socio-demographically similar women in reproductive health and HIV research.

Microbiological and Cytokine Profiling of Menstrual Blood for the Assessment of Endometrial Receptivity: A Pilot Study

Jain M et al., 2023·Biomedicines

Endometrial receptivity (ER) is a key factor required for the successful implantation of the embryo. However, the evaluation of ER is challenging, as a nondisruptive sampling of endometrial biomaterial by conventional methods is only possible outside of the embryo transfer (ET) cycle. We propose a novel approach for the assessment of ER-microbiological and cytokine profiling of menstrual blood aspirated directly from the uterine cavity at the beginning of the cryo-ET cycle. The aim of the pilot study was to evaluate its prognostic potential regarding the outcome of the in vitro fertilization procedure. Samples collected from a cohort of 42 patients undergoing cryo-ET were analyzed by a multiplex immunoassay (48 various cytokines, chemokines, and growth factors) and a real-time PCR assay (28 relevant microbial taxa and 3 members of the Herpesviridae family). Significant differences between groups of patients who achieved and did not achieve pregnancy were observed for G-CSF, GRO-α, IL-6, IL-9, MCP-1, M-CSF, SDF-1α, TNF-β, TRAIL, SCF, IP-10, and MIG (p < 0.05), whereas microbial profiles were not associated with the outcome of cryo-ET. It appeared that levels of IP-10 and SCGF-β were significantly lower (p < 0.05), in patients with endometriosis. Menstrual blood may provide great opportunities to noninvasively investigate various parameters of the endometrium.

Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for Postpartum Depression

Larsen SV et al., 2023·JAMA Psychiatry

Hormonal sensitivity may contribute to the risk of depression in some women, as observed during the premenstrual, postpartum, and perimenopausal phases, and when initiating hormonal contraception (HC). However, little evidence exists to support that such depressive episodes are linked across the reproductive life span. To determine whether prior depression associated with HC initiation is coupled with a higher risk of postpartum depression (PPD) than prior depression not associated with HC initiation. DESIGN, SETTING, This cohort study used Danish health registry data collected from January 1, 1995, through December 31, 2017, and analyzed from March 1, 2021, through January 1, 2023. All women living in Denmark born after 1978 with their first delivery between January 1, 1996, and June 30, 2017, were eligible for inclusion; 269 354 met these criteria. Women were then excluded if they had never used HC or if they had a depressive episode before 1996 or within 12 months prior to delivery. Prior depression associated with vs not associated with HC initiation, ie, if developed within 6 months after start of an HC exposure or not. Depression was defined as a hospital diagnosis of depression or filling a prescription for antidepressant medication. Crude and adjusted odds ratios (ORs) were calculated for the incidence of PPD defined as the development of depression within 6 months after first delivery. Of 188 648 first-time mothers, 5722 (3.0%) (mean [SD] age, 26.7 [3.9] years) had a history of depression associated with initiation of HC use, and 18 431 (9.8%) (mean [SD] age, 27.1 [3.8] years) had a history of depression not associated with the initiation of HC. Women with HC-associated depression had a higher risk of PPD than women with prior non-HC-associated depression (crude OR, 1.42 [95% CI, 1.24-1.64]; adjusted OR, 1.35 [95% CI, 1.17-1.56]). These findings suggest that a history of HC-associated depression may be associated with a higher risk of PPD, supporting that HC-associated depression may indicate PPD susceptibility. This finding offers a novel strategy in clinical PPD risk stratification and points to the existence of a hormone-sensitive subgroup of women.

Embryology, Week 1

Khan YS et al., 2023·StatPearls [Internet]

Human embryogenesis is a complicated process by which a fertilized egg develops into an embryo. During the first eight weeks of development, the conceptus shifts from a single-celled zygote into a multi-layered, multi-dimensional fetus with primitively functioning organs. The continued growth and increased intra-embryonic complexity during the first eight weeks of development are highly dependent upon cell signaling, proliferation, and differentiation. Due to the intricacies involved, the development of the human embryo is divided into developmental events by week. Week 1 is a major part of the germinal stage of development, a period of time that continues from fertilization through uterine implantation. Important events that occur during the first week of human embryonic development include gamete approximation, contact and fusion of gametes, fertilization, mitotic cleavage of the blastomere, morula formation, blastocyst formation, and implantation of the blastocyst.

The association between dietary patterns and risk of miscarriage: a systematic review and meta-analysis

Chung Y et al., 2023·Fertil Steril

The evidence on the association between diet and miscarriage risk is scant and conflicting. To summarize the evidence on the association between periconceptual diet and miscarriage risk in healthy women of reproductive age. Electronic databases were searched from inception to August 2022 without restriction of regions, publication types, or languages. Experimental or observational studies were considered for inclusion. The population was healthy women of reproductive age. Exposure was periconception diet. Study quality was assessed using the modified Newcastle-Ottawa Scale. Summary effect sizes (odds ratio [OR] with 95% confidence interval [CI]) were calculated for each food category. Miscarriage rate (as defined by primary studies). We included 20 studies (11 cohort and 9 case-control), of which 6 presented data suitable for meta-analysis (2 cohort and 4 case-control, n = 13,183 women). Our primary analyses suggest a reduction in miscarriage odds with high intake fruit (OR, 0.39; 95% CI, 0.33-0.46), vegetables (OR, 0.59; 95% CI, 0.46-0.76), fruit and vegetables (OR, 0.63; 95% CI, 0.50-0.81), seafood (OR, 0.81; 95% CI, 0.71-0.92), dairy products (OR, 0.63; 95% CI, 0.54-0.73), eggs (OR, 0.81; 95% CI, 0.72-0.90), and cereal (grains) (OR, 0.67; 95% CI, 0.52-0.87). The evidence was uncertain for meat, red meat, white meat, fat and oil, and sugar substitutes. We did not find evidence of an association between adherence to predefined dietary patterns and miscarriage risk. However, a whole diet containing healthy foods as perceived by the trialists, or with a high Dietary Antioxidant Index score (OR, 0.43; 95% CI, 0.20-0.91) may be associated with a reduction in miscarriage risk. In contrast, a diet rich in processed food was demonstrated to be associated with increased miscarriage risk (OR, 1.97; 95% CI, 1.36-3.34). A diet abundant in fruit, vegetables, seafood, dairy, eggs, and grain may be associated with lower miscarriage odds. Further interventional studies are required to accurately assess the effectiveness of periconception dietary modifications on miscarriage risk. CRD42020218133.

Progesterone Resistance in Endometriosis: Current Evidence and Putative Mechanisms

Zhang P et al., 2023·International journal of molecular sciences

Endometriosis is an estrogen-dependent disease characterized by the growth of endometrial-like tissue outside the uterus. Progestins are currently the most commonly used treatment for endometriosis because of their excellent therapeutic effects and limited side effects. However, progestins have been unsuccessful in some symptomatic patients. The inability of the endometrium to respond properly to progesterone is known as progesterone resistance. An increasing body of evidence suggests the loss of progesterone signaling and the existence of progesterone resistance in endometriosis. The mechanisms of progesterone resistance have received considerable scholarly attention in recent years. Abnormal PGR signaling, chronic inflammation, aberrant gene expression, epigenetic alterations, and environmental toxins are considered potential molecular causes of progesterone resistance in endometriosis. The general objective of this review was to summarize the evidence and mechanisms of progesterone resistance. A deeper understanding of how these mechanisms contribute to progesterone resistance may help develop a novel therapeutic regimen for women with endometriosis by reversing progesterone resistance.

Low-dose naltrexone for treatment of burning mouth syndrome

Sangalli L et al., 2023·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

The International Classification of Disease defines burning mouth syndrome (BMS) as a chronic intraoral burning sensation, with no identifiable local or systemic cause. Since current management is often unsatisfactory, the aim of this report is to describe a new treatment modality (i.e., low-dose naltrexone [LDN]). A 62-year-old woman presented with the complaint of burning on the tongue of 3 years' duration. Existing comorbidities were fibromyalgia, irritable bowel syndrome, headache, and interstitial cystitis. Her reported pain intensity ranged from 2/10 (morning) to 8/10 (evening) on a numeric rating scale. With the diagnosis of BMS and hyposalivation, and in light of her current clonazepam use and fibromyalgia, a dry mouth protocol and LDN (3 mg) were prescribed. After 1 month, her pain intensity decreased by 50%, with no pain upon awakening. After 2 months, the widespread pain associated with her chronic morbidities also reduced by 50%, and her headache disappeared. After adjusting LDN dose to 4.5 mg, the patient was stable at 6 months, with 50% reduction of widespread pain and 2/10 BMS pain, and no reported side effects. These preliminary results suggest that LDN may be a feasible and effective treatment for BMS, especially in patients' refractory to traditional treatment.

Laser therapy versus expectant management for selective fetal growth restriction in monochorionic twins: A systematic review

Buskmiller C et al., 2023·Prenat Diagn

Selective fetal growth restriction (sFGR) complicates 10%-26% of monochorionic twins. Treatment options include cord coagulation, expectant management, and fetoscopic laser photocoagulation. This review compared laser to expectant management for situations when cord coagulation is not an option. The MEDLINE, EMBASE, and Cochrane databases were queried for studies that compared laser to expectant management for sFGR. GRADE was used to assess quality prior to meta-analysis. A random-effects model was used to generate relative risks. Six studies were included, encompassing 299 pregnancies. One study was randomized and the remainder were retrospective cohorts. Laser is associated with more fetal deaths of the FGR twin compared to expectant management (risk ratio [RR] 2.5, 95% confidence interval [CI] 1.43-4.37, p = 0.001, I2 = 48%). Neonatal deaths and gestational age at delivery did not differ. Laser was associated with decreased abnormal neuroimaging in the AGA twin (RR 0.25, 95% CI 0.07-0.97, p = 0.05). Neurodevelopmental outcomes did not differ, although these data are limited. Laser causes more fetal deaths of the FGR twin without altering gestational age at delivery or rates of neonatal death. The literature is heterogeneous and the level of bias is high. Randomized trials that address laser for type II sFGR are needed and should include long-term neurological outcomes.

Clinical efficacy of a novel method of fertility-preserving adenomyomectomy in infertile women with diffuse adenomyosis

Yoon SH et al., 2023·Medicine (Baltimore)

Beneficial and detrimental effect of surgical adenomyomectomy is still controversial in infertile women with severely diffuse adenomyosis. The primary objective of this study was to assess whether a novel method of fertility-preserving adenomyomectomy could improve pregnancy rates. The secondary objective was to evaluate whether it could improve dysmenorrhea and menorrhagia symptoms in infertile patients with severe adenomyosis. A prospective clinical trial was conducted between December 2007 and September 2016. Fifty women with infertility due to adenomyosis were enrolled in this study after clinical assessments by infertility experts. A novel method of fertility-preserving adenomyomectomy was performed on 45 of 50 patients. The procedure included T- or transverse H-incision of the uterine serosa followed by preparation of the serosal flap, excision of the adenomyotic tissue using argon laser under ultrasonographic monitoring, and a novel technique of suturing between the residual myometrium and serosal flap. All patients obtained dysmenorrhea relief 6 months postoperatively (NRS 7.28 vs 1.56, P<.001). The amount of menstrual blood decreased significantly (140.44 vs 66.33 mL, P<.05). Of the 33 patients who attempted pregnancy postoperatively, 18 (54.5%) conceived either by natural means, in vitro fertilization and embryo transfer (IVF-ET), or thawing embryo transfer. Miscarriage occurred in 8 patients, while 10 (30.3%) had viable pregnancies. This novel method of adenomyomectomy resulted in improved pregnancy rates, as well as relief of dysmenorrhea and menorrhagia. This operation is effective in preserving fertility potential in infertile women with diffuse adenomyosis.

Fisetin, a Natural Polyphenol, Ameliorates Endometriosis Modulating Mast Cells Derived NLRP-3 Inflammasome Pathway and Oxidative Stress

Arangia A et al., 2023·Int J Mol Sci

A chronic, painful, and inflammatory condition known as endometriosis is defined by the extra-uterine development of endometrial tissue. The aim of this study was to evaluate the beneficial effects of fisetin, a naturally occurring polyphenol that is frequently present in a variety of fruits and vegetables. Uterine fragments were injected intraperitoneally to cause endometriosis, and fisetin was given orally every day. At 14 days of treatment, laparotomy was performed, and the endometrial implants and peritoneal fluids were collected for histological, biochemical, and molecular analyses. Rats subjected to endometriosis presented important macroscopic and microscopic changes, increased mast cell (MC) infiltration, and fibrosis. Fisetin treatment reduced endometriotic implant area, diameter, and volumes, as well as histological alterations, neutrophil infiltration, cytokines release, the number of MCs together with the expression of chymase and tryptase, and diminished α smooth muscle actin (α-sma) and transforming growth factor beta (TGF β) expressions. In addition, fisetin was able to reduce markers of oxidative stress as well as nitrotyrosine and Poly ADP ribose expressions and increase apoptosis in endometrial lesions. In conclusion, fisetin could represent a new therapeutic strategy to control endometriosis perhaps by targeting the MC-derived NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway and oxidative stress.

Definition and Criteria for Diagnosing Cesarean Scar Disorder

Klein Meuleman SJM et al., 2023·JAMA Netw Open

Approximately 60% of women develop a uterine niche after a cesarean delivery (CD). A niche is associated with various gynecological symptoms including abnormal uterine bleeding, pain, and infertility, but there is little consensus in the literature on the distinction between the sonographic finding of a niche and the constellation of associated symptoms. To achieve consensus on defining the clinical condition that constitutes a symptomatic uterine niche and agree upon diagnostic criteria and uniform nomenclature for this condition. Design, Setting, A consensus based modified electronic Delphi (eDelphi) study, with a predefined Rate of Agreement (RoA) of 70% or higher. Experts were selected according to their expertise with niche-related consultations, publications, and participation in expert groups and received online questionnaires between November 2021 and May 2022. Definition, nomenclature, symptoms, conditions to exclude, and diagnostic criteria of an illness caused by a symptomatic uterine niche. In total, 31 of the 60 invited experts (51.7%) participated, of whom the majority worked in university-affiliated hospitals (28 of 31 [90.3%]), specialized in benign gynecology (20 of 31 [64.5%]), and worked in Europe (24 of 31 [77.4%]). Three rounds were required to achieve consensus on all items. All participants underlined the relevance of a new term for a condition caused by a symptomatic niche and its differentiation from a sonographic finding only. Experts agreed to name this condition cesarean scar disorder, defined as a uterine niche in combination with at least 1 primary or 2 secondary symptoms (RoA, 77.8%). Defined primary symptoms were postmenstrual spotting, pain during uterine bleeding, technical issues with catheter insertion during embryo transfer, and secondary unexplained infertility combined with intrauterine fluid. Secondary symptoms were dyspareunia, abnormal vaginal discharge, chronic pelvic pain, avoiding sexual intercourse, odor associated with abnormal blood loss, secondary unexplained infertility, secondary infertility despite assisted reproductive technology, negative self-image, and discomfort during participation in leisure activities. Consensus was also achieved on certain criteria that should be met and conditions that should be excluded before making the diagnosis. In this modified Delphi study, a panel of 31 international niche experts reached consensus for the constellation of symptoms secondary to a uterine niche and named it cesarean scar disorder.

A Pilot Qualitative Case Study of Women's Experiences with Fertility Awareness-Based Methods

Capotosto MP et al., 2023·Linacre Q

This pilot qualitative case study was able to elicit rich data enabling a description of how women went through the journey of achieving pregnancy using fertility awareness-based methods. Findings underscore that women preferred using natural ways to detect ovulation and would recommend other women to do so, but with healthcare providers' guidance. The findings of this case study can serve as a starting point to provide a framework to understand women's experiences of enduring trial and error with multiple fertility awareness-based methods before discovering their effective method. Findings emphasize the importance for healthcare providers to guide women in using fertility awareness-based methods.

An Overview of Postoperative Intraabdominal Adhesions and Their Role on Female Infertility: A Narrative Review

Ghobrial S et al., 2023·Journal of clinical medicine

Postoperative intraabdominal adhesions can occur after more than 90% of gynecologic surgeries. They not only cause chronic pelvic pain and small bowel obstruction, but are also one of the main reasons for infertility. Adhesions are not only a burden for the affected patients, but are also a burden for the healthcare system, since the treatment of adhesion-associated complications costs a considerable amount of money. The gold standard for the diagnosis of adhesions is by laparoscopy, although other methods, such as transvaginal hydro-laparoscopy, are being discussed as better alternatives. Ideally, adhesions are avoided inherently, by operating carefully and by using microsurgical principles. If this is not possible, gel barriers have been shown to be successful in reducing postoperative adhesions.

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Rahmioglu N et al., 2023·Nat Genet

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

Fallopian tube recanalization for the management of infertility

Roberts A, 2023·CVIR Endovasc

Infertility is a world-wide problem, defined as failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse. There are multiple causes for infertility involving both male and female factors. Fallopian tube occlusion is a common reason for female infertility. The initial attempts to treat proximal obstruction involved the use of a whalebone bougie positioned in the uterine cornua to dilate the proximal tube by Smith as early as 1849. Fluoroscopic fallopian tube recanalization for the treatment of infertility was first described in 1985. Since that time, there have been over 100 papers describing various methods for recanalization of occluded fallopian tubes. Fallopian tube recanalization is a minimally invasive procedure which is performed on an outpatient basis. It should be a first line therapy for patients with proximal occlusion of fallopian tubes.

Pelvic Inflammatory Disease

Jennings LK et al., 2023·StatPearls [Internet]

Pelvic inflammatory disease (PID) is defined as an inflammation of the upper genital tract due to an infection in women. The disease affects the uterus, fallopian tubes, and/or ovaries. It is typically an ascending infection, spreading from the lower genital tract. The majority of cases of PID are related to a sexually transmitted infection. The diagnosis of PID is primarily clinical and should be suspected in female patients with lower abdominal or pelvic pain and genital tract tenderness. During the patient’s evaluation, other etiologies of pain, including ectopic pregnancy, should be considered and ruled out. PID is treated with antibiotics to cover the primary pathogens, including Neisseria gonorrhoeae and Chlamydia trachomatis. Short-term complications include tubo-ovarian or pelvic abscess. Long-term complications include ectopic pregnancy, infertility, and chronic pelvic pain. Early diagnosis and treatment can potentially prevent complications.

Efficacy of N-Acetylcysteine on Endometriosis-Related Pain, Size Reduction of Ovarian Endometriomas, and Fertility Outcomes

Anastasi E et al., 2023·International journal of environmental research and public health

Endometriosis is a chronic, estrogen-dependent, inflammatory disease, whose pivotal symptoms are dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Besides the usual medical treatments, recent evidence suggests there are potential benefits of oral N-acetylcysteine (NAC) on endometriotic lesions and pain. The primary objective of this prospective single-cohort study was to confirm the effectiveness of NAC in reducing endometriosis-related pain and the size of ovarian endometriomas. The secondary objective was to assess if NAC may play a role in improving fertility and reducing the Ca125 serum levels. Patients aged between 18-45 years old with a clinical/histological diagnosis of endometriosis and no current hormonal treatment or pregnancy were included in the study. All patients received quarterly oral NAC 600 mg, 3 tablets/day for 3 consecutive days of the week for 3 months. At baseline and after 3 months, dysmenorrhea, dyspareunia and CPP were assessed using the Visual Analog Scale score (VAS), while the size of the endometriomas was estimated through a transvaginal ultrasound. Analgesics (NSAIDs) intake, the serum levels of Ca125 and the desire for pregnancy were also investigated. Finally, the pregnancy rate of patients with reproductive desire was evaluated. One hundred and twenty patients were recruited. The intensity of dysmenorrhea, dyspareunia and CPP significantly improved (p < 0.0001). The use of NSAIDs (p = 0.001), the size of the endometriomas (p < 0.0001) and the serum levels of Ca125 (p < 0.0001) significantly decreased. Among the 52 patients with reproductive desire, 39 successfully achieved pregnancy within 6 months of starting therapy (p = 0.001). Oral NAC improves endometriosis-related pain and the size of endometriomas. Furthermore, it decreases Ca125 serum levels and may improve fertility in patients with endometriosis.

Reproductive surgery: revisiting its origins and role in the modern management of fertility

Bortoletto P et al., 2023·Fertil Steril

For years, reproductive surgery was the mainstay of reproductive care. With the evolution and ultimate success of in vitro fertilization (IVF), reproductive surgery became an adjuvant therapy, indicated mainly for severe symptoms or to enhance success rates with assisted reproductive technologies. As success rates for IVF have plateaued, and emerging data rekindles the enormous benefits of surgically correcting reproductive pathologies, there is renewed interest among reproductive surgeons in reviving research and surgical expertise in this area. In addition, new instrumentation and surgical techniques to preserve fertility have gained traction and will solidify the need to have skilled reproductive endocrinology and infertility surgeons in our practice.

Association of hormonal and reproductive risk factors with breast cancer in Indian women: A systematic review of case-control studies

Maurya AP et al., 2023·Indian J Cancer

The incidence of breast cancer in India has seen a rapid increase in recent years. Hormonal and reproductive risk factors for breast cancer have been affected by socioeconomic development. Studies on breast cancer risk factors in India are limited by the small sample size and specific geographical area. The current systematic review was carried out to assess the association of hormonal and reproductive risk factors with breast cancer in Indian women. A systematic review of MEDLINE, Embase, Scopus, and Cochrane database of systematic reviews were done. Relevant case-control studies published in peer-reviewed indexed journals were analyzed for hormonal risk factors such as age at menarche, menopause, and first childbirth; breastfeeding; abortion; and oral contraceptive pills use. Younger age (<13 years) at menarche was associated with high risk (odds ratio 1.23-3.72). Other hormonal risk factors with strong association were age at first childbirth and menopause, parity, and duration of breastfeeding. Abortion and the use of contraceptive pills did not have a clear association with breast cancer. Hormonal risk factors have a higher association in premenopausal disease and estrogen receptor-positive tumors. There is a strong association between hormonal and reproductive risk factors and breast cancer in Indian women. The protective effect of breastfeeding is related to the cumulative duration of breastfeeding.

Screening of regulated aromatic amines in clothing marketed in Brazil and Spain: Assessment of human health risks

Souza MCO et al., 2023·Environmental Research

Azo dyes used in textile products contain aromatic amines (AAs), which may be released into the environment after skin bacteria cleavage the azo bond. In Europe, 22 carcinogenic AAs are regulated. Unfortunately, no information is available in many non-European countries, including Brazil. This study aimed to determine the concentrations of 20 regulated AAs in clothes marketed in Brazil and Spain. Generally, higher levels of regulated AAs were found in samples sold in Brazil than in Spain, which is linked to the lack of regulation. Sixteen AAs showed concentrations above 5 mg/kg in samples commercialized in Brazil, while 11 exceeded that threshold in Spain. Regulated AAs with levels above 5 mg/kg were more found in synthetic clothes of pink color. Concentrations in clothing were also used to evaluate the dermal exposure to AAs in 3 vulnerable population groups. The highest exposure corresponded to 2,4-diaminoanisole for toddlers in Brazil and 4,4-oxydianiline for newborns in Spain. Non-cancer risks associated with exposure to 4,4-benzidine by Brazilian toddlers was 14.5 (above the threshold). On the other hand, 3,3-dichlorobenzidine was associated with potential cancer risks for newborns and toddlers in Brazil. Given this topic's importance, we recommend conducting continuous studies to determine the co-occurrence of carcinogenic substances.

Sexual and reproductive health experiences and care of adult women with cystic fibrosis

Kazmerski TM et al., 2023·J Cyst Fibros

As survival and health improve in people with cystic fibrosis (CF), more women with CF (wwCF) are considering their sexual and reproductive health (SRH). This study compared SRH experiences, behaviors, and care utilization of wwCF to the general population and defined CF-impacted considerations and care preferences. We surveyed wwCF aged ≥25 years regarding SRH and compared results to the US National Survey of Family Growth (NSFG;n = 4357) and friend controls(n = 123). We used descriptive statistics and chi-squared/Fisher's exact testing and linear regression for comparisons. A total of 460 wwCF (mean age 36.1 years) completed the survey. WwCF were less likely to report current contraceptive use (43%vs76% NSFG, p<0.001;60% friends, p = 0.005). Nearly 25% of wwCF reported worsened CF symptoms during their menstrual cycles, 50% experienced urinary incontinence, and 80% vulvovaginal candidiasis. WwCF were significantly less likely to be parents (46%vs62% friends, p = 0.015) and to have experienced pregnancy (37%vs78% NSFG, p<0.001;58% friends, p = 0.002). More wwCF required medical assistance to conceive (29%vs12% NSFG, p<0.001 and 5% friends, p<0.001). Eighty-four percent of wwCF view their CF doctor as their main physician and 41% report no primary care provider (vs19% friends; p<0.001). WwCF report suboptimal rates of contraceptive and preconception counseling/care and are less likely to have received HPV vaccination (42%vs55%friends, p = 0.02). Despite desiring SRH conversations with their CF team, <50% report discussing SRH topics. WwCF have significantly different SRH experiences than non-CF peers. They report suboptimal SRH care compared to their preferences highlighting an urgent need to encourage SRH counseling/care in the CF model.

Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case-control study and meta-analysis

Fitzpatrick D et al., 2023·PLoS medicine

Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations. Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case-control study for 9,498 women aged <50 years with incident invasive breast cancer diagnosed in 1996 to 2017, and for 18,171 closely matched controls. On average, 7.3 (standard deviation [SD] 4.6) years of clinical records were available for each case and their matched controls prior to the date of diagnosis. Conditional logistic regression yielded odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by the hormonal contraceptive type last prescribed, controlled for age, GP practice, body mass index, number of recorded births, time since last birth, and alcohol intake. MEDLINE and Embase were searched for observational studies published between 01 January 1995 and 01 November 2022 that reported on the association between current or recent progestagen-only contraceptive use and breast cancer risk in premenopausal women. Fixed effects meta-analyses combined the CPRD results with previously published results from 12 observational studies for progestagen-only preparations. Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk. This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years.

Successful Implementation of Menstrual Cycle Biomarkers in the Treatment of Infertility in Polycystic Ovary Syndrome-Case Report

Kicińska AM et al., 2023·Healthcare (Basel)

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Absent, impaired, or rare ovulation induces progesterone deficiency in the luteal phase, which is a critical problem in PCOS. A usual pattern of progesterone administration from a fixed and arbitrary pre-determined day of a menstrual cycle may preserve infertility but can easily be avoided. We present the case of a 29-year-old infertile woman who had been ineffectively treated for over two years. We introduced a line of therapy that was suited to her individual menstrual cycle by implementing biomarker recording. Supplementation based on a standardized observation of the basal body temperature (BBT) and cervical mucus stopped the vicious circle of absent ovulation and hyperandrogenism, restoring regular bleeding, ovulation cycles, and fertility. The implementation of a reliable fertility awareness method (FAM), accompanied by a standardized teaching methodology and periodic review of the observations recorded by the patient, validated through an ultrasound examination and plasma gonadotropins, estrogens, and progesterone concentrations, is key to achieving therapeutic success. The presented case is an example of a clinical vignette for many patients who have successfully managed to improve their fertility and pregnancy outcomes by applying the principles of a personalized treatment approach together with gestagens by recording their fertility biomarkers.

A Comparison of Two Hormonal Fertility Monitoring Systems for Ovulation Detection: A Pilot Study

Mu Q et al., 2023·Medicina (Kaunas)

Accuracy in detecting ovulation and estimating the fertile window in the menstrual cycle is essential for women to avoid or achieve pregnancy. There has been a rapid growth in fertility apps and home ovulation testing kits in recent years. Nevertheless, there lacks information on how well these apps perform in helping users understand their fertility in the menstrual cycle. This pilot study aimed to evaluate and compare the beginning, peak, and length of the fertile window as determined by a new luteinizing hormone (LH) fertility tracking app with the Clearblue Fertility Monitor (CBFM). A total of 30 women were randomized into either a quantitative Premom or a qualitative Easy@Home (EAH) LH testing system. The results of the two testing systems were compared with the results from the CBFM over three menstrual cycles of use. Potential LH levels for estimating the beginning of the fertile window were calculated along with user acceptability and satisfaction. The estimates of peak fertility by the Premom and EAH LH testing were highly correlated with the CBFM peak results (R = 0.99, p < 0.001). The participants had higher satisfaction and ease-of-use ratings with the CBFM compared to the Premom and EAH LH testing systems. LH 95% confidence levels for estimating the beginning of the fertile window were provided for both the Premom and EAH LH testing results. Our pilot study findings suggest that the Premom and EAH LH fertility testing app can accurately detect impending ovulation for women and are easy to use at home. However, successful utilization of these low-cost LH testing tools and apps for fertility self-monitoring and family planning needs further evaluation with a large and more diverse population.

Oral contraceptive pill (OCP) treatment alters the gene expression of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) in polycystic ovary syndrome (PCOS) women compared to drug-naive PCOS women

Yousuf SD et al., 2023·BMC Women's Health

Background Polycystic ovary syndrome (PCOS) presents clinical symptoms of menstrual abnormalities, excessive hair growth (hirsutism), scalp hair loss, acne and infertility. Metabolic abnormalities such as obesity, insulin resist‑ ance, glucose intolerance and cardiovascular problems constitute an essential part of PCOS, all of which can have significant long-term health consequences. Low-grade chronic inflammation demonstrated by persistent moderately elevated serum levels of inflammatory and coagulatory markers plays a critical role in the pathogenesis of PCOS. Oral contraceptive pills (OCPs) constitute the mainstay of pharmacologic therapy for women with PCOS to regularize cyclicity and ameliorate androgen excess. On the other hand, OCP use is associated with various venous thromboem‑ bolic and proinflammatory events in the general population. PCOS women always carriers the increased lifetime risk of these events. The studies on the effect of OCPs on inflammatory, coagulation and metabolic parameters in PCOS are less robust. Therefore in this study, we investigated and compared the messenger RNA (mRNA) expression profiles of genes implicated in inflammatory and coagulation pathways between drug-naive and OCP-treated PCOS women. The selected genes include intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), mono‑ cyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1). Furthermore, the correlation between the selected markers and various metabolic indices in the OCP group has also been explored. Method The relative amounts of ICAM-1, TNF-α, MCP-1 and PAI-1 mRNA in peripheral blood mononuclear cells from 25 drug-naive PCOS subjects (controls) and 25 PCOS subjects who received OCPs containing 0.03 mg-ethinyl-estra‑ diol and 0.15 mg-levonorgestrel for at least six months (cases) were estimated using real-time qPCR. The statistical Open Access Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases, involving 6–20% percent of women of reproductive age [ 1 ], with an even greater incidence among Kashmiri women [ 2 ]. Apart from the symptoms of hyperandrogenism and infertility, PCOS is associated with several metabolic abnormalities, including obesity, insulin resistance (IR), hyperlipidemia, systemic inflammation and functional atherosclerosis [ 3 – 5 ]. Elevated inflammatory and coagulatory markers characterize this low-grade inflammation and endothelial dysfunction. Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) are potent biological markers for the development of inflammatory and metabolic diseases which may include PCOS [ 6 – 8 ]. ICAM-1 belongs to the super immunoglobulin family and is produced mainly on cell surfaces of endothelial cells, smooth muscle cells, macrophages and activated lymphocytes. It is required for the adhesion of freely moving leukocytes to blood vessel walls and trans-endothelial migration to the vascular intima. This action is crucial in the evolution of atheroma from early to advanced stages. Cleavage of membranebound ICAM-1 results in circulating soluble ICAM-1 (sICAM-1) [ 9 , 10 ]. In prospective epidemiologic investigations, its levels in serum have been linked to abdominal obesity, insulin resistance and cardiovascular disease (CVD) [ 11 ]. TNF-α, a cytokine released by adipose tissue, instigates insulin resistance. In the endothelium, the TNF-α signaling pathway, which is regulated by nuclear factor kappa B (NF-KB), governs the expression of adhesion molecules such as sICAM-1 [ 12 ]. Many studies have found that women with PCOS have significantly higher ICAM-1, MCP-1 and TNF-α than women without PCOS [ 13 , 14 ]. interpretation was conducted using SPSS version 20.0 (SPSS, Inc, Chicago, IL), Epi Info version 2002 (Disease Control and Prevention Centres, Atlanta, GA) and GraphPad Prism 5 (GraphPad Software, La Jolla, CA) software. Result Six months of OCP therapy enhanced the expression of inflammatory genes viz ICAM-1, TNF-α and MCP-1 mRNA in PCOS women by 2.54, 2.05 and 1.74 folds, respectively, in this study. However, PAI-1 mRNA in the OCP group showed no significant increase. Furthermore, in cases, ICAM-1 mRNA expression positively correlated with body mass index (BMI) (p = 0.01), fasting insulin (p = 0.01), insulin 2 h p = 0.02), glucose 2 h (p = 0.01) and triglycerides (p = 0.01). TNF-α mRNA expression positively correlated with fasting insulin (p = 0.0007). MCP-1 mRNA expression positively cor‑ related with (BMI) (p = 0.002). Conclusion OCPs helped reduce clinical hyperandrogenism and regularise menstrual cycles in women with PCOS. [truncated]

Investigation of He's Yang Chao recipe against oxidative stress-related mitophagy and pyroptosis to improve ovarian function

Miao C et al., 2023·Front Endocrinol (Lausanne)

Primary ovarian insufficiency (POI) is a common gynecological disease with serious ramifications including low pregnancy rate and low estrogen symptoms. Traditional Chinese medicine is regarded as an effective treatment for POI. However, the therapeutic mechanism of it is unclear. In this study, a mouse model of primary ovarian insufficiency was established by intraperitoneal injection of cyclophosphamide (CTX) and He's Yang Chao Recipe (HSYC) concentrate was used for intragastric administration. Serum hormone levels (Anti-Müllerian Hormone, Estradiol, Progesterone, Luteinizing Hormone and Follicle Stimulating Hormone) and Oxidative Stress (OS) related products, superoxide dismutase (SOD), GSH-Px, and malondialdehyde (MDA) were measured by enzyme-linked immunosorbent assay. Pathological changes in ovarian tissue were evaluated by hematoxylin and eosin staining, and flow cytometry was used to determine reactive oxygen species content and mitochondrial membrane potential levels in granulosa cells. Mitochondrial distribution and morphology were investigated using immunofluorescence staining. The level of mitophagy was evaluated by LC3 immunofluorescence staining and autophagosome counts using electron microscopy. Western blotting and qPCR were used to detect the expression of proteins and genes related to mitophagy and the NLRP3 inflammasome. After HSYC treatment, the ovarian damage was milder than in the CTX group. Compared with the CTX group; SOD, GSH-Px, and the total antioxidant capacity were significantly increased, while MDA and ROS were decreased in the HSYC treatment groups. Furthermore, mitochondrial distribution and membrane potential levels were improved after HSYC treatment compared to the CTX group. After the HSYC treatment, the LC3 fluorescent intensity and autophagosome counts were decreased. Similarly, mitophagy related markers PINK1, Parkin, LC3, and Beclin1 were decreased, while p62 was significantly increased, compared with the CTX groups. The mRNA and protein expression of NLRP3 inflammasome, NLRP3, caspase-1, GSDMD, IL-18, and IL-1β were significantly decreased in the HSYC treatment groups. This is the first study in molecular mechanisms underlying HSYC against granulosa cell injury in POI. HSYC protects ovaries from CTX-induced ovarian damage and oxidative stress. HSYC enhanced ovarian function in mice with primary ovarian insufficiency by inhibiting PINK1-Parkin mitophagy and NLRP3 inflammasome activation.

Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?

Cho L et al., 2023·Circulation

Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women's health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk.

Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics

Singh S et al., 2023·Journal of clinical medicine

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, typically characterized by anovulation, infertility, obesity, insulin resistance, and polycystic ovaries. Lifestyle or diet, environmental pollutants, genetics, gut dysbiosis, neuroendocrine alterations, and obesity are among the risk factors that predispose females to PCOS. These factors might contribute to upsurging metabolic syndrome by causing hyperinsulinemia, oxidative stress, hyperandrogenism, impaired folliculogenesis, and irregular menstrual cycles. Dysbiosis of gut microbiota may play a pathogenic role in the development of PCOS. The restoration of gut microbiota by probiotics, prebiotics, or a fecal microbiota transplant (FMT) might serve as an innovative, efficient, and noninvasive way to prevent and mitigate PCOS. This review deliberates on the variety of risk factors potentially involved in the etiology, prevalence, and modulation of PCOS, in addition to plausible therapeutic interventions, including miRNA therapy and the eubiosis of gut microbiota, that may help treat and manage PCOS.

Synchronization of the ovulation and copulation timings increased the number of in vivo fertilized oocytes in superovulated female mice

Nakao S et al., 2023·PLoS One

The number of sperm that reaches the oocytes in mammalian species is limited. In mice, 8-10 oocytes are ovulated, a similar number of sperm reaches the oocytes, and nearly all oocytes are fertilized via natural mating. Meanwhile, our improved superovulation technique (ultrasuperovulation: administration of inhibin antiserum and equine chorionic gonadotropin [IASe]) produced 100 oocytes from a single female C57BL/6 mouse but resulted in only approximately 20 fertilized oocytes via mating. We hypothesized that sperm shortage in the ampulla might cause this low fertilization rate. Mice were mated in the proestrus stage or after hormone injection, but ovulation timing was not considered. In clinical application, the rhythm method supports fertilization by testing the ovulation period and synchronizing the ovulation and copulation timings. Therefore, this study examined the effects of ovulation and copulation timings on in vivo fertilization in female mice with IASe. Synchronization of the ovulation and copulation timings increased fertilization efficiency in female mice with ultrasuperovulation. The number of embryos obtained post ovulation was three times higher than that obtained pre ovulation. This study suggests that synchronized ovulation and copulation timings improve the efficiency of in vivo fertilization in IASe-treated female mice. This technique can be used to produce genetically modified mice and develop technologies for infertility treatment.

Diagnosis and management of isthmocele (Cesarean scar defect): a SWOT analysis

Dominguez JA et al., 2023·Ultrasound Obstet Gynecol

The purpose of this State-of-the-Art Review was to provide a strategic analysis, in terms of strengths, weaknesses, opportunities and threats (SWOT analysis), of the current evidence regarding the management of uterine isthmocele (Cesarean scar defect). Strengths include the fact that isthmocele can be diagnosed on two-dimensional transvaginal ultrasound, and that surgical repair may restore natural fertility potential and prevent secondary infertility, as well as reduce the risk of miscarriage and other obstetric complications. However, there is a lack of high-quality evidence regarding the best diagnostic method and criteria, as well as the potential benefits of surgical repair with respect to fertility. There is a need for experienced surgeons skilled in the various isthmocele repair techniques. Isthmocele repair does not prevent the need for Cesarean delivery in subsequent pregnancies. There is increasing awareness regarding the accuracy of transvaginal ultrasound in diagnosing isthmocele. This may lead to surgical correction and prevention of obstetric and perinatal complications in subsequent pregnancies, including Cesarean scar pregnancy. Regarding threats, the existence of different surgical techniques means that there is a risk of selecting an inadequate approach if the type of isthmocele and the patient's characteristics are not considered. There is a risk of overtreatment when asymptomatic defects are repaired surgically. Finally, there is an absence of cost-effectiveness analyses to justify routine repair. Thus, while there are many data suggesting that isthmocele has an adverse effect on both natural fertility and the outcome of assisted reproduction techniques, high-quality evidence to support surgical isthmocele repair in all asymptomatic patients desiring future fertility are lacking. There is increasing agreement to recommend hysteroscopic repair of isthmocele as a first-line approach as long as the residual myometrial thickness is at least 2.5-3.0 mm.

Influence of Vitamin D supplementation on reproductive outcomes of infertile patients: a systematic review and meta-analysis

Meng X et al., 2023·Reproductive biology and endocrinology : RB&E

Low vitamin D status has been associated with an increased risk for infertility. Recent evidence regarding the efficacy of vitamin D supplementation in improving reproductive outcomes is inconsistent. Therefore, this systematic review was conducted to investigate whether vitamin D supplementation could improve the reproductive outcomes of infertile patients and evaluate how the parameters of vitamin D supplementation affected the clinical pregnancy rate. We searched seven electronic databases (CNKI, Cqvip, Wanfang, PubMed, Medline, Embase, and Cochrane Library) up to March 2022. Randomized and cohort studies were collected to assess the reproductive outcomes difference between the intervention (vitamin D) vs. the control (placebo or none). Mantel-Haenszel random effects models were used. Effects were reported as odds ratio (OR) and their 95% confidence interval (CI). PROSPERO CRD42022304018. Twelve eligible studies (n = 2352) 9 randomized controlled trials (RCTs, n = 1677) and 3 cohort studies (n = 675). Pooled results indicated that infertile women treated with vitamin D had a significantly increased clinical pregnancy rate compared with the control group (OR: 1.70, 95% CI: 1.24-2.34; I2 = 63%, P = 0.001). However, the implantation, biochemical pregnancy, miscarriage, and multiple pregnancy rates had no significant difference (OR: 1.86, 95% CI: 1.00-3.47; I2 = 85%, P = 0.05; OR: 1.49; 0.98-2.26; I2 = 63%, P = 0.06; OR: 0.98, 95% CI: 0.63-1.53; I2 = 0%, P = 0.94 3.64, 95% CI: 0.58-11.98; I2 = 68%, P = 0.21). The improvement of clinical pregnancy rate in the intervention group was influenced by the vitamin D level of patients, drug type, the total vitamin D dosage, the duration, administration frequency, and daily dosage of vitamin D supplementation. The infertile women (vitamin D level < 30 ng/mL) treated with the multicomponent drugs including vitamin D (10,000-50,000 IU or 50,000-500,000 IU), or got vitamin D 1000-10,000 IU daily, lasting for 30-60 days could achieve better pregnancy outcome. To the best of our knowledge, this is the first meta-analysis systematically investigated that moderate daily dosing of vitamin D supplementation could improve the clinical pregnancy rate of infertile women and reported the effects of vitamin D supplementation parameters on pregnancy outcomes. A larger sample size and high-quality RCTs are necessary to optimize the parameters of vitamin D supplementation to help more infertile patients benefit from this therapy.

Lower anti-Müllerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women

Clara E Van Ommen et al., 2023·AIDS

We sought to better understand factors associated with ovarian aging in women with HIV (WWH). HIV has been associated with diminished fertility, younger age at menopause, and shorter leukocyte telomere length (LTL), a marker of cellular aging. We herein examine cross-sectional and longitudinal associations between LTL, anti-Müllerian hormone (AMH), and HIV. We included WWH and HIV-negative women 12-50 years of age in the CARMA cohort with one or more study visit(s). LTL and AMH were measured by qPCR and ELISA, respectively. Women were analyzed in peak reproductive (<35 years) vs. late reproductive (≥35 years) life phases. Using multivariable mixed-effect linear or logistic regressions, we assessed factors associated with AMH and ΔAMH/year while adjusting for relevant confounders. WWH had shorter LTL and lower AMH levels compared to HIV-negative controls despite being of similar age. After adjusting for relevant factors, HIV was associated with 20% lower AMH levels in women under 35 years of age and shorter LTL was associated with AMH levels below 2 ng/ml among women aged 35 years or older. Longitudinally, ΔAMH/year was largely related to initial AMH level among older women, and to age in younger women. Factors associated with AMH change across women's reproductive lifespan. Lower AMH among peak reproductive aged WWH suggests that HIV may have an initial detrimental effect on ovarian reserve, an observation that may warrant counseling around pregnancy planning. In women aged 35 years or older, the association between shorter LTL and lower AMH suggests that the immune and reproductive aging connections are more important in this age group.

In vitro fertilization increases the odds of gestational diabetes: a nationwide register-based cohort study

Vaajala M et al., 2023·Acta diabetologica

Risk of Hypertensive Disorders in Pregnancy After Fresh and Frozen Embryo Transfer in Assisted Reproduction: A Population-Based Cohort Study With Within-Sibship Analysis

H Petersen S et al., 2023·Hypertension (Dallas, Tex. : 1979)

Frozen embryo transfer (frozen-ET) is increasingly common because of improved cryopreservation methods and elective freezing of all embryos. Frozen-ET is associated with higher risk of hypertensive disorders in pregnancy than both natural conception and fresh embryo transfer (fresh-ET), but whether this is attributable to parental factors or treatment is unknown. Using the Medical Birth Registries of Denmark (1994-2014), Norway, and Sweden (1988-2015), linked to data from national quality registries and databases on assisted reproduction, we designed a population-based cohort study with within-sibship comparison. We included 4 426 691 naturally conceived, 78 300 fresh-ET, and 18 037 frozen-ET singleton pregnancies, of which 33 209 sibships were conceived using different conception methods. Adjusted odds ratios (aOR) of hypertensive disorders in pregnancy for fresh-ET and frozen-ET versus natural conception with 95% CI were estimated using multilevel logistic regression, where random effects provided conventional population-level estimates and fixed effects gave within-sibship estimates. Main models included adjustment for birth year, maternal age, parity, and country. Risk of hypertensive disorders in pregnancy was higher after frozen-ET compared to natural conception, both at population-level (7.4% versus 4.3%, aOR, 1.74 [95% CI, 1.61-1.89]) and within sibships (aOR, 2.02 [95% CI, 1.72-2.39]). For fresh-ET, risk was similar to natural conception, both at population-level (aOR, 1.02 [95% CI, 0.98-1.07]) and within sibships (aOR, 0.99 [95% CI, 0.89-1.09]). Frozen-ET was associated with substantially higher risk of hypertensive disorders in pregnancy, even after accounting for shared parental factors within sibships.

Development of a nutrition screening tool to identify need for dietetic intervention in female infertility

Deepak Kumar K et al., 2023·Journal of human nutrition and dietetics : the official journal of the British Dietetic Association

One in seven couples are impacted by infertility in the UK, and female infertility is often associated with several health conditions impacted by nutrition. Despite many studies aimed at identifying the critical role of nutrition in infertility, there is currently no screening tool that identifies nutritional risk factors for infertility. To propose a self-administered screening tool to identify women who would benefit from nutritional intervention to promote fertility. A narrative review was carried out to identify and summarise modifiable nutritional risk factors that can influence female fertility, including comorbidities that can influence nutrition intake, absorption, and metabolism. A nutrition screening tool outlining modifiable nutrition risk factors potentially improving female fertility has been proposed, comprising of BMI, medical history and quality of diet and lifestyle which would aid in designing evidence based dietetic services for female infertility.