Human Fertilisation and Embryology Authority, 2021
# Multiple births in fertility treatment 2019
UK multiple February 2022
[Download the underlying dataset as Excel Worksheet](https://www.hfea.gov.uk/media/ikninm5o/2022-01-25-multiple-births-in-fertility-treatment-underlying-supplementary-data-tables.xlsx "2022 01 25 Multiple Births In Fertility Treatment Underlying Supplementary Data Tables").
## - [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#main-points)
- [History of multiple births in the UK](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#history-of-multiple-births-in-the-uk)
- [Section 1. Multiple births reduced following cross-sector collaborative efforts](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-1)
- [Section 2. Single embryo transfers increased most among young patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-2)
- [Section 3. Largest improvements in multiple birth rate among youngest and oldest patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-3)
- [Section 4. Multiple embryo transfers put younger patients at greatest risk of multiple birth](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-4)
- [Section 5. Greater risk of multiple births when using donor eggs](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-5)
- [Section 6. Multiple birth rates higher among Black patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/multiple-births-in-fertility-treatment-2019/#section-6)
- [Section 7. Higher multiple birth rate...
Lisova KM et al., 2021·Journal of medicine and life
The purpose of the study was TO analyze the fetoplacental complex hormone levels and changes in their dynamics in pregnant women with miscarriage and the impact of these features on the subsequent course of pregnancy. Hormone levels were determined at different stages of gestation in 50 healthy women with a physiological course of pregnancy (control group) and 50 pregnant women with a history of miscarriage (main group). The women of the main group had a significantly slower rate of increase in hormones and a lag in quantitative indicators than the control group. The estradiol level indicators were 4.1 times (76.0%) and 2.89 times (65.5%) lower in women with miscarriage in the embryonic and late fetal period, respectively, compared to healthy women. Indicators of the level of placental lactogen and chorionic gonadotropin in the embryonic period in women with miscarriage were lower by 39.1% and 50.9%, respectively, compared to healthy women. In the late fetal period, the level of these hormones was lower by 72.9% and 35.4%, respectively. In the embryonic and late fetal periods, progesterone levels were lower by 67.4% and 68.4%, respectively, compared to the control group. The data obtained are evidence of a pronounced hormonal abnormality of the placenta, and hence a marker of fetoplacental dysfunction, which on the background of miscarriage develops at the early stages and continues to progress with the course of pregnancy.
Guo Y et al., 2021·Evidence-based complementary and alternative medicine : eCAM
Endometriosis (EM) is a common and benign estrogen-dependent gynecological disorder among women of reproductive age, and secondary dysmenorrhea is one of the more severe symptoms. However, the mechanism behind the development of dysmenorrhea is poorly understood, and there is a lack of effective methods for diagnosing and treating EM dysmenorrhea. In this regard, complementary and alternative medicine (CAM) has recently come into widespread use due to its limited adverse reactions and high efficiency. This review updates the progress of CAM in the treatment of EM dysmenorrhea and seeks to identify the therapeutic efficacy as well as the mechanisms behind these effects based on the available clinical and experimental studies. According to the literature, CAM therapy for EM dysmenorrhea, including herbs (herbal prescriptions, extracts, and patents), acupuncture, and Chinese herbal medicine enema (CHM enema), is effective for relieving dysmenorrhea with fewer unpleasant side effects when compared to hormonal and surgical treatments. In addition, we discuss and analyze the existing gaps in the literature. We hope to provide some instructive suggestions for clinical treatment and experimental research in the future.
Human Fertilisation and Embryology Authority, 2021
# Impact of COVID-19 on fertility treatment 2020
UK statistics for IVF and DI treatment, May 2022
[Download the underlying dataset as Excel Worksheet](https://www.hfea.gov.uk/media/rhih4yyx/impact-of-covid-19-on-fertility-treatment-2020-underlying-dataset.xlsx "Impact of COVID-19 on fertility treatment 2020 - Underlying dataset").
## - [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#main-points)
- [Foreword](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#foreword)
- [HFEA regulatory response to the COVID-19 pandemic](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#hfea-regulatory-response-to-the-covid-19-pandemic)
- [1\. NHS-funded IVF treatment slower to recover](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#section-1)
- [2\. Treatments decreased by 20% from 2019 to 2020](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#section-2)
- [3\. Greater decrease in IVF cycles among younger patients and patients in heterosexual relationships](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#section-3)
- [4\. Egg donor registrations decreased by 23% from 2019 to 2020](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#section-4)
- [5\. Impact of COVID-19 varied by nation and English region](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertility-treatment-2020/#section-5)
- [6\. COVID-19 caused delays in GP appointments and fertility treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/impact-of-covid-19-on-fertil...
Areta JL et al., 2021·European journal of applied physiology
Energy availability (EA) is defined as the amount of dietary energy available to sustain physiological function after subtracting the energetic cost of exercise. Insufficient EA due to increased exercise, reduced energy intake, or a combination of both, is a potent disruptor of the endocrine milieu. As such, EA is conceived as a key etiological factor underlying a plethora of physiological dysregulations described in the female athlete triad, its male counterpart and the Relative Energy Deficiency in Sport models. Originally developed upon female-specific physiological responses, this concept has recently been extended to males, where experimental evidence is limited. The majority of data for all these models are from cross-sectional or observational studies where hypothesized chronic low energy availability (LEA) is linked to physiological maladaptation. However, the body of evidence determining causal effects of LEA on endocrine, and physiological function through prospective studies manipulating EA is comparatively small, with interventions typically lasting ≤ 5 days. Extending laboratory-based findings to the field requires recognition of the strengths and limitations of current knowledge. To aid this, (1) provide a brief historical overview of the origin of the concept in mammalian ecology through its evolution of algebraic calculations used in humans today, (2) Outline key differences from the 'energy balance' concept, (3) summarise and critically evaluate the effects of LEA on tissues/systems for which we now have evidence, hormonal milieu, reproductive system endocrinology, bone metabolism and skeletal muscle; and finally (4) provide perspectives and suggestions for research upon identified knowledge gaps.
NaProTECHNOLOGYEffectiveness and EthicsDiagnostic Applications
NaProTECHNOLOGY – a chance for offspring or fraud? In the media space in Poland, you can meet the concept of Naprotechnology as an alternative to the in vitro procedure. Often, many myths and untruths appear in the discussion regarding this method of treatment. Naprotechnology is a new look at the health of women and men created by prof. Thomas Hilgers. It takes into account natural fertility biomarkers thanks to observation with the Creighton Model based on the female mucus. At every stage of diagnosis and treatment, Naprotechnology respects human life from the moment of conception and the mutual dignity of the spouses. It also does not use assisted reproductive procedures for ethical reasons. Naprotechnology is part of the broader scientific discipline of restorative medicine in infertility. Thanks to the accurate diagnosis and observation of the cycle, it is possible to correctly diagnose the cause of infertility. A proper diagnosis is the starting point for the implementation of specialized pharmacological and surgical treatment for both women and men. Properly used Naprotechnology and restorative medicine are highly effective in treating marital infertility. W przestrzeni medialnej w Polsce można spotkać pojęcie Naprotechnologii jako alternatywy dla procedury in vitro. Często w dyskusji pojawia się wiele mitów i nieprawdy dotyczących takiego sposobu leczenia. Naprotechnologia, stworzona przez prof. Thomasa Hilgersa, jest nowym spojrzeniem na zdrowie kobiety i mężczyzny. Uwzględnia ona naturalne biomarkery płodności dzięki obserwacji za pomocą Modelu Creighton bazującego na kobiecym śluzie. Na każdym etapie diagnostyki i leczenia Naprotechnologia szanuje ludzkie życie od samego poczęcia oraz wzajemną godność małżonków. Nie stosuje ona też procedur wspomaganego rozrodu z powodów etycznych. Naprotechnologia jest częścią szerszej dyscypliny naukowej, jaką jest przyczynowe leczenie niepłodności. Dzięki dokładnej diagnostyce i obserwacji cyklu możliwe jest postawienie prawidłowej diagnozy dotyczącej przyczyny niepłodności. Właściwa diagnoza jest punktem wyjścia dla wdrożenia specjalistycznego leczenia farmakologicznego i chirurgicznego zarówno wobec kobiety, jak i mężczyzny. Prawidłowo stosowana Naprotechnologia i przyczynowe leczenie niepłodności cechują się wysoką skutecznością leczenia niepłodności małżeńskiej.
Agence de la biomédecine, 2021·Agence de la biomédecine
Rapport annuel d'AMP Vigilance 2020 publié par l'Agence de la biomédecine. Document de surveillance pour les activités d'Assistance Médicale à la Procréation en France couvrant les incidents et effets indésirables. Annual AMP (Medically Assisted Reproduction) Vigilance Report 2020 from the French Agence de la biomédecine, the national mandatory ART registry covering adverse events and safety surveillance for licensed AMP activities in France.
The neuropeptide oxytocin acts as a hormone and a neuromodulator, influencing a multitude of human social behaviors, including reproduction. During childbirth and the postpartum period, it plays a key role in regulating and controlling processes that ensure a safe birth and the health of mother and child. Especially the onset of labor, the progress of labor and initial breastfeeding are mediated by oxytocin. In the maternal brain it controls the initiation of the mother-infant bond and the mother's emotional responses towards her child. In this review we summarize the current state of knowledge about the role of oxytocin during the different aspects and mechanisms of human childbirth, combining research from human and animal studies. Physiological and psychological stress during childbirth and lactation can have negative effects on the progress of labor, breastfeeding and bonding. We discuss how maternity caregivers can support the positive effects of oxytocin and minimize the effects of stress. Furthermore, we highlight aspects of the basic neurobiological principles and connections where further research is needed to improve our understanding of the regulation and the effects of oxytocin to support maternal and infant health.
The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated. The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. (Table 1) This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm. (Figure 1) The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.
In elite athletes, training individualization is widely recommended to optimize competitive performance. Previous studies have evidenced the impact of hormonal fluctuations on different performance parameters among female athletes. While consideration of menstrual cycle (MC) phases as a parameter in training individualization strategies is necessary, systematic evidence identifying such impacts in elite athletes should be evaluated. Systematically review publications that have investigated the link between MC phases and performance in elite female athletes. The overarching aim is to identify whether a consensus across studies exists enabling evidence-based recommendations for training individualization depending on menstrual cycle phases. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three major scientific publication databases were searched from inception until November 3, 2020. Studies included focused on the influence of physiological or psychological parameters throughout at least one phase of the menstrual cycle of elite athletes. A total of 780 search results were yielded and 26 references from a past bibliography were added manually. About 662 papers were reviewed of which 218 studies were assessed for eligibility. Of these, only seven (1%) precisely investigated the influence of a performance or physical parameter during at least one menstrual cycle phase. These seven studies included a total of 314 elite female participants (20.58 ± 1.91 years). Three used interviews, questionnaires or prospective analyses of reports. Four conducted several performance tests or included physical measures although only two performed tests during training or before/during competition. Among the seven studies, five performed hormonal testing through sampling of blood, saliva, or urine. The remaining relied on athletes' menstruation diaries. The current evidence suggests a variable association between menstrual cycle and a few performance-related outcomes, such as endurance or power resistance, ligament stiffness, decision making skills, psychology, or competitiveness. Different sports performance-related parameters are affected during the menstrual cycle among elite athletes, but the parameters themselves and the magnitude and the direction of the effects are inconclusive. Additional longitudinal and prospective studies to systematically monitor on-field performance parameters are urgently required in order to enable recommendations and training individualization in female elite athletes.
Zipper R et al., 2021·Women's health reports (New Rochelle, N.Y.)
Chronic pelvic pain (CPP) is a common and debilitating condition that affects millions of U.S. women. Most treatments are ineffective and innovative new therapies are desperately needed. Large, controlled studies show that photobiomodulation (PBM) can reduce pain in patients with other chronic pain conditions, such as low back pain, neck pain, and fibromyalgia. The objective of this pilot study was to determine if transvaginal PBM (TV-PBM) can reduce pain in women with CPP. We conducted a before and after, observational, pilot study. Patients completed the Short Form-McGill Pain Questionnaire (SF-MPQ) at baseline, 1 week, 3 months, and 6 months after nine treatments of TV-PBM. Clinicians completed the Clinical Global Impression Scale (CGI) assessing patient illness severity at the same time. Wilcoxon rank-sum t-tests and effect size using Cohen's d coefficient (low effect size if d < 0.2, medium if 0.2 < d > 8, and high if d > 0.8) was used to measure degree of pain improvement, which was also considered clinically significant if pain reduction was >30%. Thirteen women completed 9 treatments, and 10 women were successfully followed to 6 months. At baseline, the mean SF-MPQ score was 19.7 (standard deviation [SD] ± 5.9). Compared with baseline, 60% improved; the mean SF-MPQ score decreased to 10.0 (SD ±7.5, p = 0.004, d = 1.6) at 1 week after treatment, to 9.7 (SD ±7.9, p = 0.005, d = 1.7) at 3 months, and 8.2 (SD ±8.1, p = 0.002, d = 1.9) at 6 months. Transvaginal PBM provided significant and sustained pain relief to women with CPP up to 6 months. Further controlled studies are needed to confirm these findings, however, in this initial pilot, TV-PBM shows promise.
The reference range and potential value of inhibin B are still unclear and controversial. This study aimed to define the variation trend of inhibin B in healthy women with age and explore its value in the reflection of ovarian reserve. A total of 2524 healthy reproductive age women from eight medical institutes nationwide were recruited. The variation tendency of inhibin B with age was primarily established in the first group of 948 women and validated in another 605. We evaluated the relationship between inhibin B and classic ovarian reserve and function markers. The potency of inhibin B in predicting AFC <5-7 was also estimated and compared with FSH. The nomogram showed that serum levels of inhibin B rapidly decreased after the age of 40. Inhibin B was positively correlated with AMH (R = 0.57, P < 0.001), AFC (R = 0.34, P < 0.001) and testosterone (R = 0.10, P = 0.002), and negatively correlated with FSH (R = -0.41, P < 0.001) and LH (R = -0.20, P < 0.001) and FSH/LH (R=-0.18, P < 0.001), while no correlation was found with PRL. Unexpectedly, Inhibin B (AUC = 0.74, P < 0.001 for the establishment population; AUC = 0.78, P < 0.001 for the validation population) had a slightly higher value than FSH (AUC = 0.71, P < 0.001 for the establishment population; AUC = 0.72, P < 0.001 for the validation population) in diagnosing AFC <5-7. For healthy reproductive age women, the decline of inhibin B can reflect decreased ovarian reserve effectively, having a good consistency with AMH and AFC. More importantly, inhibin B had an advantage in predicting AFC <5-7 compared with FSH, which suggested the potential of inhibin B in predicting ovarian response.
Ovarian tissue cryopreservation is considered as a useful option to preserve fertility for cancer patients. This study purposed to evaluate the change of telomere length and senescence markers during human ovarian tissue cryopreservation. Ovarian tissues were obtained from women who underwent benign ovarian surgery in the gynecology research unit of a university hospital with prior consent and IRB approval. DNA was extracted from the ovarian tissues using a DNeasy tissue kit and telomere lengths in the DNA samples were determined by real time PCR before and after cryopreservation. All tissues were stained with hematoxylin-eosin and subjected to immunohistochemistry and TUNEL assays. Other senescence markers, including p53, p16, p21, and phospho-pRb proteins, were evaluated using western blot analysis. Ovarian tissues were collected from ten patients and prepared for slow freezing with the same size of diameter 4 mm and 1 mm thickness. Mean age of patients was 26.7 ± 6.2 years (range, 16-34 years), and ovarian tissues were cryopreserved and thawed 4 weeks after cryopreservation. The mean telomere length was significantly decreased after cryopreservation (9.57 ± 1.47 bp vs. 8.34 ± 1.83 bp, p = 0.001). Western blot analysis revealed that p53, p16, and p21 proteins increased and phospho-pRb protein expression decreased after ovarian tissue cryopreservation. Ovarian tissue cryopreservation and transplantation is regarded as one of promising options for fertility preservation. However, clinicians and researchers should be aware of possible irreversible DNA changes such as shortening of telomere length and alterations of other senescence markers in human ovarian tissues.
What were the utilization, effectiveness and safety of practices in assisted reproductive technologies (ART) globally in 2014 and what global trends could be observed? The estimated total number of ART cycles conducted in 76 participating countries in 2014 was 1.93 million representing ∼66% of global activity, with 5-year trends including an increase in success rates and proportion of frozen embryo transfer (FET) cycles, improvement in cumulative live birth rates per aspiration, a continued increase in single embryo transfer (SET) and thus a reduction in multiple birth rates, an increase in preimplantation genetic testing and stabilization in the use of intracytoplasmic sperm injection (ICSI). ART is widely practiced throughout the world but continues to be characterized by significant disparities in utilization, practice, effectiveness and safety. The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) annual world report series provides an important instrument for tracking trends in ART treatment and for providing clinical and public health data to ART professionals, health authorities, patients and the general public. STUDY DESIGN, SIZE, A retrospective, cross-sectional survey on ART procedures performed globally during 2014 was carried out. A new method for calculating ART utilization rates and number of babies born was introduced in this latest ICMART world report. PARTICIPANTS/MATERIALS, SETTING, Overall, 76 countries and 2 746 ART centres submitted data through national and regional ART registries on ART cycles performed during 2014 and their treatment and pregnancy outcomes. ART cycles and outcomes are described at a country level, regionally and globally. Aggregate country data are processed and analyzed based on methods developed by ICMART. MAIN A total of 1 629 179 ART cycles were reported for the treatment year 2014. After imputing data for missing values and non-reporting centres in reporting countries, an estimated 1 929 905 cycles resulted in >439 039 babies in reporting countries. From 2010 to 2014, the number of reported non-donor aspirations and FET cycles increased by 37.3% and 67.5%, respectively. The proportion of women aged ≥40 years undergoing non-donor ART increased from 23.2% in 2010 to 27.0% in 2014. ICSI, as a percentage of non-donor aspiration cycles, remained relatively stable at 64.8%. The IVF/ICSI combined delivery rates per fresh aspiration and FET cycle were 19.9% and 24.3%, respectively. In fresh non-donor cycles, SET increased from 30.0% in 2010 to 40.0% in 2014, while the average number of transferred embryos decreased from 1.95 to 1.73-but with wide country variation. The rate of twin deliveries following fresh non-donor transfers continued to decrease, from 20.4% in 2010 to 16.2% in 2014, and the triplet rate decreased from 1.1% to 0.5%. In FET non-donor cycles in 2014, the SET rate was 61.6%, with an average of 1.43 embryos transferred, resulting in twin and triplet rates of 10.1% and 0.2%, respectively. The cumulative delivery rate per aspiration increased from 27.1% in 2010 to 32.1% in 2014. The overall perinatal mortality rate per 1 000 births was 19.4 following fresh IVF/ICSI cycles and 9.5 following FET cycles. Among reporting countries, oocyte donation cycles represented 7.3% of all embryo transfers (89 751 transfer cycles) and resulted in 39 278 babies. LIMITATIONS, The data presented are dependent on the quality and completeness of data submitted by individual countries to ICMART directly or through regional registries. This report covers approximately two-thirds of world ART activity. China is a major contributor of global cycles missing from this report. Continued efforts to improve the quality and consistency of ART data reported by registries are still needed, including the use of internationally agreed standard definitions (The International Glossary of Infertility and Fertility Care). A new method was introduced in this report to calculate ART utilization and number of babies born following ART; therefore, these results are not directly comparable with previous reports. The ICMART world reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment effectiveness and safety continue to increase globally, the wide disparities in access to treatment, procedures performed and embryo transfer practices warrant attention by clinicians and policymakers. The new method for estimating ART utilization and number of babies born provided more conservative estimates compared to the previuos method. STUDY FUNDING/COMPETING INTEREST(S): ICMART receives unrestricted grants from Abbott and Ferring Pharmaceuticals. ICMART also acknowledges financial support from the following organization
To report the utilization, effectiveness, and safety of practices in assisted reproductive technology (ART) globally in 2013 and assess global trends over time. Retrospective, cross-sectional survey on the utilization, effectiveness, and safety of ART procedures performed globally during 2013. Seventy-five countries and 2,639 ART clinics. PATIENT(S): Women and men undergoing ART procedures. INTERVENTION(S): All ART. MAIN OUTCOME MEASURE(S): The ART cycles and outcomes on country-by-country, regional, and global levels. Aggregate country data were processed and analyzed based on methods developed by the International Committee for Monitoring Assisted Reproductive Technology (ICMART). RESULT(S): A total of 1,858,500 ART cycles were conducted for the treatment year 2013 across 2,639 clinics in 75 participating countries with a global participation rate of 73.6%. Reported and estimated data suggest 1,160,474 embryo transfers (ETs) were performed resulting in >344,317 babies. From 2012 to 2013, the number of reported aspiration and frozen ET cycles increased by 3% and 16.4%, respectively. The proportion of women aged >40 years undergoing nondonor ART increased from 25.2% in 2012 to 26.3% in 2013. As a percentage of nondonor aspiration cycles, intracytoplasmic sperm injection (ICSI) was similar to results for 2012. The in vitro fertilization (IVF)/ICSI combined delivery rates per fresh aspiration and frozen ET cycles were 24.2% and 22.8%, respectively. In fresh nondonor cycles, single ET increased from 33.7% in 2012 to 36.5% in 2013, whereas the average number of transferred embryos was 1.81-again with wide country variation. The rate of twin deliveries after fresh nondonor transfers was 17.9%; the triplet rate was 0.7%. In frozen ET cycles performed in 2013, single ET was used in 57.6%, with an average of 1.49 embryos transferred and twin and triplet rates of 10.8% and 0.4%, respectively. The cumulative delivery rate per aspiration was 30.4%, similar to that in 2012. Perinatal mortality rate per 1,000 births was 22.2% after fresh IVF/ICSI and 16.8% after frozen ET. The data presented depended on the quality and completeness of the data submitted by individual countries. This report covers approximately two-thirds of world ART activity. Continued efforts to improve the quality and consistency of reporting ART data by registries are still needed. CONCLUSION(S): Reported ART cycles, effectiveness, and safety increased between 2012 and 2013 with adoption of a better method for estimating unreported cycles.
PCOSProgesterone TherapyAnti-Androgen TherapyFeasibility and Pilot Studies
Androgenic Polycystic Ovary Syndrome (PCOS) creates physical/emotional burdens in 4-20% of premenopausal women living with PCOS (WLWP) few menstruations per year, subfertility, hirsutism/acne and low quality of life by validated PCOS Questionnaire (PCOSQ). Combined hormonal contraceptives (CHC), the current standard-of-care, improve PCOSQ only 16%; with stopping CHC, benefits disappear within 6-months. We hypothesize too-fast brain/luteinizing hormone (LH) pulses cause PCOS. Progesterone (P4) slows LH when testosterone (FreeT) is normal. Combining two approved medications, Cyclic P4 with anti-androgen, Spironolactone (Sp), will likely provide effective, durable benefits. WLWP lit-review suggested significant P4 7-14-day benefits. A 6-month prospective feasibility study of CyclicP4/Sp is necessary. Perform a pilot study in 40 WLWP on Cyclic P4 (300 mg/bedtime, 14 days/month) plus Spironolactone (Sp, 200 mg/d). Assess longitudinal within-WLWP 6-month 1) PCOSQ; 2) FreeT, HbA1c, and LH; plus 3) WLWP's acceptance of CyclicP4/Sp. Single-centre, prospective, longitudinal single cohort study. Recruit \~7-8 WLWP/month over 4-6 months; 85% retention. Eligible WLWP have physician-diagnosed PCOS, are 1-month off CHC/metformin, ages 19-35 (avoiding adolescence/perimenopause), HbA1c <6.4% (no diabetes) and commit to non-hormonal contraception, if needed. Recruitment uses online, internet, strategic ads and tear-tab posters. Measures at 0 and 6 as above plus K+ (safety assessment). Menstrual Cycle Diary monitoring (flow, adherence), 2 visits, monthly telephone/emails for support and assessment of any adverse effects. changes by paired T-test.
A feasibility 6-month study of CyclicP4/Sp will facilitate a CIHR-funded RCT of CHC versus this innovative and likely beneficial treatment for WLWP.
Dorani F et al., 2021·Journal of psychiatric research
This is the first study to assess the prevalence of symptoms of premenstrual dysphoric disorder (PMDD), episodes of postpartum depression symptoms (PPD) after first childbirth, and climacteric mood symptoms in Attention-Deficit/Hyperactivity Disorder (ADHD). 209 consecutive women (18-71 years) with ADHD completed the PMDD chapter of the Neuropsychiatric Interview Plus version 5.0.0 to assess PMDD, the Edinburgh Postnatal Depression Scale to assess PPD, and the Greene Climacteric Scale to assess climacteric symptoms. Comorbid psychiatric disorders, medication use, and chronobiological sleep characteristics were also assessed. The prevalence of PMDD and PPD were high in ADHD, compared to the general population. PMDD symptoms were associated with less use of contraceptives. Antidepressants were associated with more PMDD symptoms. The following GCS scores anxiety, depression, and sexual dysfunction, vasomotor and somatic complaints. No significant differences were found in sleep characteristics or current comorbidity between the groups with and without PPD or PMDD, or increased climacteric scores. The prevalences of PMDD, PPD and climacteric scores were high in women with ADHD. This is the first study in women with ADHD that suggests that female ADHD patients suffer from significant PMDD symptoms, experience PPD during the first child birth, and experience more severe climacteric symptoms.
Sims ST et al., 2021·BMJ open sport & exercise medicine
As the number of female athletes competing rises globally, training methodologies should reflect sex differences across critical metrics of adaptation to training. Surrogate markers of the autonomic nervous system (ANS) used for monitoring training load are heart rate variability (HRV) and resting heart rate (RHR). The aim was to investigate ovarian hormone effects on standard recovery metrics (HRV, RHR, respiratory rate (RR) and sleep duration) across a large population of female athletes. A retrospective study analysed 362 852 days of data representing 13 535 menstrual cycles (MC) from 4594 respondents (natural MC n=3870, BC n=455, progestin-only n=269) for relationships and/or differences between endogenous and exogenous ovarian hormones on ANS. HRV and return to baseline (recovery) decreased as resting HR and RR increased (p<0.001) from the early follicular to the late luteal phase of the MC. Patterning was paradoxical across phases for users of combined hormonal contraception (BC) as compared with the patterning of the MC. HRV and recovery start elevated and drop off quickly during the withdrawal bleed, rising through the active pill weeks (p<0.001). Progestin-only users had similar patterning as the MC. The relationship between normalised recovery and previous day strain is modulated by birth control type. BC exhibited steeper declines in recovery with additional strain-normalised recovery decreases by an additional 0.0055±0.00135 (p<0.001) per unit of strain; with no significant difference between MC and progestin-only (p=0.19). The patterning of ANS modulation from ovarian hormones is significantly different between naturally cycling women and those on BC, with the patterning dependent on the type of contraception used.
Fertility AwarenessApp-Based MethodsFertility Awareness MethodsProspective Cohort Study
Digital fertility awareness-based methods of birth control are an attractive alternative to hormonal or invasive birth control for modern women. They are also popular among women who may be planning a pregnancy over the coming years and wish to learn about their individual menstrual cycle. The aim of this study was to assess the effectiveness of the Natural Cycles app at preventing pregnancy for a cohort of women from the United States and to describe the key demographics of current users of the app in such a cohort. This prospective real-world cohort study included users who purchased an annual subscription to prevent pregnancy. Demographics were assessed through answers to in-app questionnaires. Birth control effectiveness estimates for the entire cohort were calculated using 1-year pearl index (PI) and 13-cycle cumulative pregnancy probability (Kaplan-Meier life table analysis). The study included 5879 women who contributed an average of 10.5 months of data for a total of 5125 woman-years of exposure. The average user was 30 years old with a body mass index of 24 and reported being in a stable relationship. With typical use, the app had a 13-cycle cumulative pregnancy probability of 7.2% and a 1-year typical use PI of 6.2. When the app was used under perfect use, the PI was 2.0. The data presented in this study give insights into the cohort of women using this app in the United States, and provide country-specific effectiveness estimates. The contraceptive effectiveness of the app was in line with previously published figures from Natural Cycles (PI of seven for typical use and two for perfect use).
Incidence, risk factors, and perinatal morbidity and mortality rates related to amniotic fluid embolism remain a challenge to evaluate, given the presence of differing international diagnostic criteria, the lack of a gold standard diagnostic test, and a significant overlap with other causes of obstetric morbidity and mortality. The aims of this study were (1) to analyze the clinical features and outcomes of women using the largest United States-based contemporary international amniotic fluid embolism registry, and (2) to investigate differences in demographic and obstetric variables, clinical presentation, and outcomes between women with typical versus atypical amniotic fluid embolism, using previously published and validated criteria for the research reporting of amniotic fluid embolism. The AFE Registry is an international database established at Baylor College of Medicine (Houston, TX) in partnership with the Amniotic Fluid Embolism Foundation (Vista, CA) and the Perinatology Research Branch of the Division of Intramural Research of the NICHD/NIH/DHHS (Detroit, MI). Charts submitted to the registry between August 2013 and September 2017 were reviewed, and cases were categorized into typical, atypical, non-amniotic fluid embolism, and indeterminate, using the previously published and validated criteria for the research reporting of AFE. Demographic and clinical variables, as well as outcomes for patients with typical and atypical AFE, were recorded and compared. Student t tests, χ(2) tests, and analysis of variance tables were used to compare the groups, as appropriate, using SAS/STAT software, version 9.4. A total of 129 charts were available for review. Of these, 46% (59/129) represented typical amniotic fluid embolism and 12% (15/129) atypical amniotic fluid embolism, 21% (27/129) were non-amniotic fluid embolism cases with a clear alternative diagnosis, and 22% (28/129) had an uncertain diagnosis. Of the 27 women misclassified as an amniotic fluid embolism with an alternative diagnosis, the most common actual diagnosis was hypovolemic shock secondary to postpartum hemorrhage. Ten percent (6/59) of the women with typical amniotic fluid embolism had a pregnancy complicated by placenta previa, and 8% (5/61) had undergone in vitro fertilization to achieve pregnancy. In all, 66% (49/74) of the women with amniotic fluid embolism reported a history of atopy or latex, medication, or food allergy, compared to 34% of the obstetric population delivered at our hospital over the study period (P < .05). Our data represent a series of women with amniotic fluid embolism whose diagnosis has been validated by detailed chart review, using recently published and validated criteria for research reporting of amniotic fluid embolism. Although no definitive risk factors were identified, a high rate of placenta previa, reported allergy, and conceptions achieved through in vitro fertilization was observed.
Function of the lower extremities after prenatal myelomeningocele (MMC) repair is best assessed with ambulatory function at 30-36 months of age, but parents often ask about function before this milestone. Lower extremity movement can be assessed by ultrasound (US) and at the newborn exam (NE), but correlation between US, NE, and ambulation is not firmly established. This was a retrospective correlation study of fetuses that underwent open prenatal MMC repair at SSM Cardinal Glennon Fetal Care Institute, St. Louis, MO, between January 2011 and June 2017. Movement at the ankles, knees, and hips was assessed by US after open repair on postoperative days (PODs) 0-5 and at 32 weeks gestation. NE was performed by physical therapy or neurosurgery within the first month of life, and pediatric follow-up between 30 and 36 months of age was obtained to document ambulation. Forty-two fetuses were included. Joint movement it was present on POD 1 in 7% of fetuses and 62% by POD 5. Degree of ventriculomegaly, lesion level, and lesion length did not have a significant effect on US, NE, or ambulation. Knee movement on POD 3 correlated with knee movement at NE (k = 0.58, p < 0.01), but only later knee movement correlated with ambulation (k = 0.28-0.46, p = 0.01). Hip movement at 32 weeks was the only single joint assessment that correlated with NE and ambulation (k = 0.45 and 0.46, p = 0.03 and 0.01, respectively). Lower extremity movement increases between POD 1 and POD 5 in fetuses after open fetal MMC repair. Knee and hip movement on US at 32 weeks correlates with ambulation at 30-36 months. These data may inform counseling, and direct therapy and spark prospective investigations.
To examine potential risk factors associated with the success rate following fallopian tube recanalization (FTR) in infertile women with obstruction of the proximal fallopian tube. We retrospectively studied patients who underwent FTR for tubal obstructive infertility between January 2016 and December 2018 at the Third Affiliated Hospital of Guangzhou Medical University. FTR was performed using a catheter and guidewire system to clear tubal obstruction. Predictive factors potentially associated with the success rate were assessed by logistic regression. A total of 762 patients were included. Multivariable analysis showed that age (odds ratio [OR] = 2.38, 95% confidence interval [CI]: 1.24-4.58), infertility type (OR = 2.82, 95% CI: 1.36-6.21), history of ectopic pregnancy (OR = 7.87, 95% CI: 4.05-15.81), history of abdominal surgery (OR = 4.30, 95% CI: 2.22-8.60), history of artificial abortion curettage (OR = 4.08, 95% CI: 2.12-8.03), and duration of infertility (OR = 2.03, 95% CI: 1.06-3.85) were independently associated with postoperative tubal patency. Our findings suggest that risk factors, such as age ≥35 years, secondary infertility, duration of infertility ≥5 years, and histories of ectopic pregnancy, abdominal surgery, and artificial abortion curettage, affect the success rate of FTR. These factors may also predict surgical success in treating tubal obstructive infertility.
Chaer R et al., 2020·Diseases (Basel, Switzerland)
Reproductive health is compromised during anorexia nervosa (AN). However, it is still unclear whether this medical complication is reversible after recovery from AN. The purpose of this paper was to conduct a systematic review of the major reproductive health outcomes in females after recovery from AN. The review was conducted in adherence to preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines. Data were collated using meta-analysis and a narrative approach. Of the 1186 articles retrieved, five studies met the inclusion criteria and were reviewed. These studies monitored weight-restored females who had recovered from AN for a follow-up period of between six and 18 years. Their narrative analysis revealed that appropriate treatment of AN leads to the normalization of reproductive function, especially in terms of fertility, pregnancy, and childbirth rates. The meta-analysis confirmed this finding, where the pooled odds of childbirth rates between the AN group and the general population was not statistically significant (OR = 0.75, 95% CI: 0.43-1.29, p = 0.41). We conclude that if patients undergo appropriate eating-disorder treatment and weight restoration, it appears to be unlikely that reproductive health is affected by AN. However, since this finding is derived from only a few studies, it requires replication and confirmation.
Contraception/ComparisonReproductive Endocrinology
Open Access
Sex steroid hormones potently shape brain functions, including those critical to maintain mental health such as serotonin signaling. Use of oral contraceptives (OCs) profoundly changes endogenous sex steroid hormone levels and dynamics. Recent register-based studies show that starting an OC is associated with increased risk of developing depression. Here, we investigate whether use of OCs in healthy women is associated with a marker of the serotonin system in terms of serotonin 4 receptor (5-HT4R) brain imaging. [(11)C]SB207145-PET imaging data on 53 healthy women, of whom 16 used OCs, were available from the Cimbi database. We evaluated global effects of OC use on 5-HT4R binding in a latent variable model based on 5-HT4R binding across cortical and subcortical regions. We demonstrate that OC users have 9-12% lower global brain 5-HT4R binding potential compared to non-users. Univariate region-based analyses (pallidostriatum, caudate, hippocampus, amygdala, anterior cingulate cortex, and neocortex) supported the global effect of OC use with the largest difference present in the hippocampus (-12.8% (95% CI [-21.0; -3.9], P(corrected) = 0.03). We show that women who use OCs have markedly lower brain 5-HT4R binding relative to non-users, which constitutes a plausible molecular link between OC use and increased risk of depressive episodes. We propose that this reflects a reduced 5-HT4R gene expression, possibly related to a blunted ovarian hormone state among OC users.
Despite the available research investigating uterine physiology during and immediately following pregnancy, including at the vascular and muscular levels, knowledge of the potential long-term timeline of such changes is limited. Thus, our study sought to investigate the potential long-term changes in uterine vasculature and horn length in the postpartum rat, following delivery and weaning. Female Long-Evans rats (n = 9-11 rats/group/timepoint) a pregnant group and an age-matched virgin control group. Rat weight, food consumption and vaginal impedance measurements were recorded throughout the experiment. Rats in the pregnant group were bred and pregnancy was confirmed using ultrasound imaging. The uterus and its vasculature were collected at various 3 (week of weaning), 8-9 and 13 weeks postpartum, and at age-equivalent timepoints in the virgin group, and the diameters of the main uterine artery and vein, and lengths of the mesometrial segmental vessels (MSV) and uterine horns were recorded. The results indicated a significant difference between the previously-pregnant and virgin rats in both internal and external arterial diameters (but not arterial wall thickness), as well as the uterine horn length, 3 weeks postpartum, but not 8-9 and 13 weeks postpartum. Significant differences were observed in both venous diameter and MSV length at all timepoints measured. Placental scars were also observed in previously-pregnant rats at all timepoints measured. Our study highlights the long-term impact of pregnancy on the uterine vasculature and the necessity for consideration of such changes on subsequent pregnancies, as well as pregnancy-related vascular pathologies.
Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). MAIN The viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the SPIRIT statement, and over 80 specialty journals, including Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set.
The 2018 Assisted Reproductive Technology (ART) Fertility Clinic Success Rates Report, prepared under the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493), presents data submitted to the Centers for Disease Control and Prevention (CDC) by 456 reporting fertility clinics in the United States, Puerto Rico, and the District of Columbia for ART cycles initiated during the 2018 reporting year. The report includes 203,119 ART cycles, 73,831 live-birth deliveries, and 81,478 infants born through ART. Clinic-specific data are presented for each reporting clinic and include fresh and frozen ART cycles using patients' own eggs and donor eggs, broken out by patient age band (less than 35, 35 to 37, 38 to 40, 41 to 42, and over 42 years). The 2018 Report introduced data suppression rules to suppress the publication of small numbers (1 through 4) to reduce the risk of patient identification. The Report also presents national summary figures and clinic table summaries, including cumulative success rates that combine fresh and frozen embryo transfers from a single oocyte retrieval. CDC estimates that the proportion of all ART cycles reported to the National ART Surveillance System (NASS) represents 97 to 98 percent of all ART cycles performed in the United States.
Samartzis EP et al., 2020·Annals of translational medicine
Endometriosis is a benign gynecologic condition affecting up to one woman out of ten of reproductive age. It is defined by the presence of endometrial-like tissue in localizations outside of the uterine cavity. It often causes symptoms such as chronic pain, most frequently associated with the menstrual cycle, and infertility, but may also be oligo- or asymptomatic. There is evidence that some ovarian carcinoma (OC) histotypes, mainly the ovarian clear cell (OCCC) and endometrioid (EnOC) carcinoma, may arise from endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interacting domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which frequently co-occur. In ARID1A deficient cancers preclinical experimental data suggest different targetable mechanisms including epigenetic regulation, cell cycle, genomic instability, the PI3K/AKT/mTOR pathway, inflammatory pathways, immune modulation, or metabolic alterations as potential precision oncology approaches. Most of these strategies are relying on the concept of synthetic lethality in which tumors deficient in ARID1A are more sensitive to the different compounds. Some of these approaches are currently being or have recently been investigated in early clinical trials. The remarkably frequent occurrence of these mutations in endometriosis-associated ovarian cancer, the occurrence in a relatively young population, and the high proportion of platinum-resistant disease certainly warrants further investigation of precision oncology opportunities in this population. Furthermore, advanced knowledge about oncogenic mutations involved in endometriosis-associated ovarian carcinomas may be potentially useful for early cancer detection. However, this approach may be complicated by the frequent occurrence of somatic mutations in benign endometriotic tissue as recent studies suggest. In this narrative review of the current literature, we will discuss the data available on endometriosis-associated ovarian carcinoma, with special emphasis on epidemiology, diagnosis and molecular changes that could have therapeutic implications and clinical applicability in the future.
Rondanelli M et al., 2020·Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
Boron is a trace element that plays an important role in numerous biological functions, including calcium metabolism, growth and maintenance of bone tissue. However, there are still no precise indications regarding a possible role of boron supplementation, and its amount of supplementation, to maintain bone health. So the aim of this narrative review was to consider the state of the art on the effectiveness of boron supplementation (alone or with other micronutrients) on growth and maintenance of bone in humans through control of calcium, vitamin D and sex steroid hormone metabolism in order to suggest a daily dosage of boron supplementation. This review included 11 7 regarding the supplementation with boron alone and 4 regarding supplementation with boron and other nutrients. Despite the number of studies considered being low, the number of subjects studied is high (594) and the results are interesting. The studies considered in this narrative review have evaluated the positive effectiveness on bone, in humans, through control of calcium, vitamin D and sex steroid hormone metabolism, considering a dietary supplementation of 3 mg/day of boron (alone or with other nutrients); this supplementation is demonstrably useful to support bone health (in order to prevent and maintain adequate bone mineral density), also considering the daily dose of 3 mg is much lower than the Upper Level indicated by EFSA in the daily dose of 10 mg.
Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org et al., 2020·Fertility and sterility
Ovarian reserve is defined as the number of oocytes remaining in the ovary, or oocyte quantity (oocyte number). Markers of ovarian reserve include hormone levels and sonographically measured features of the ovaries. These markers can be useful as predictors of oocyte yield following controlled ovarian stimulation and oocyte retrieval. However, they are poor predictors of reproductive potential independently from age. This document replaces the document of the same name last published in 2012 (Fertil Steril 2012;98:1407-15).
Bariani MV et al., 2020·Current opinion in endocrinology, diabetes, and obesity
Uterine leiomyoma (fibroids) is a gynecologic disorder impacting the majority of women in the United States. When symptomatic, these noncancerous tumors can cause severe morbidity including pelvic pain, menorrhagia, and infertility. Endocrine-disrupting chemicals (EDCs) may represent a modifiable risk factor. The aim of this review is to summarize recent human and experimental evidence on EDCs exposures and fibroids. Multiple EDCs are associated with fibroid outcomes and/or processes including phthalates, parabens, environmental phenols, alternate plasticizers, Diethylstilbestrol, organophosphate esters, and tributyltin. Epidemiologic studies suggest exposure to certain EDCs, such as di-(2-ethylhxyl)-phthalate (DEHP), are associated with increased fibroid risk and severity. Both human and experimental studies indicate that epigenetic processes may play an important role in linking EDCs to fibroid pathogenesis. In-vitro and in-vivo studies show that DEHP, bisphenol A, and diethylstilbestrol can impact biological pathways critical to fibroid pathogenesis. While research on EDCs and fibroids is still evolving, recent evidence suggests EDC exposures may contribute to fibroid risk and progression. Further research is needed to examine the impacts of EDC mixtures and to identify critical biological pathways and windows of exposure. These results could open the door to new prevention strategies for fibroids.
This study aims to evaluate the effects of myo-inositol supplementation on gestational diabetes mellitus (GDM) rates and body water distribution in overweight non-obese women. 223 overweight non-obese women pregnant were randomly assigned to the treatment group (2 g of myo-inositol plus 200 µg of folic acid) or to the placebo one (200 µg of folic acid). The treatment lasted until three weeks after delivery. A tetrapolar impedance analyser was used to study body composition. The incidence of GDM was significantly reduced in the myo-inositol group compared with the placebo group. There was a significant increase in TBW, ECW and ICW values in the placebo group compared to the myo-inositol group. We have recorded a significant reduction in the overall incidence of pregnancy-induced hypertension in the myo-inositol group compared with the placebo group. Our results demonstrate the effectiveness of myo-inositol supplementation in preventing GDM in overweight non-obese pregnant women.
Infertility affects one in 16 married women in the United States where 12.7% of these seek treatment. The stress of infertility and treatment is known to impact marital satisfaction, which can be further complicated by personal and religious beliefs regarding the ethics of some assistive reproductive technologies. A morally acceptable approach to infertility diagnosis and treatment is natural procreative technology or NaProTECHNOLOGY (NPT) using the Creighton Model FertilityCare™ System. A quantitative, descriptive study utilizing demographic surveys and the Index of Marital Satisfaction found that couples using NPT reported marital satisfaction.
While we agree with many of the points stated by Dyer et al. in their recent commentary inRBMO(Dyer et al., 2020), we believe their conclusions are focused too narrowly. Limiting the indicator of access to, and utilization of, fertility treatment to assisted reproductive technology (ART) excludes information that is of key importance for subfertile couples, populations, and policymakers. Even in countries where access to ART is widespread, there are more births in subfertile couples through non-ART treatment than through ART (Stanford et al., 2016).
While ART is necessary for some couples to have a child, it is not required for many subfertile couples, and overuse of ART may potentially be harmful (Annual Capri Workshop Group 2019). Focusing solely on ART as a metric may unnecessarily encourage overutilization (Boltz et al., 2017).
We believe the focus on ART and its outcomes for national and international registries of fertility treatment has stunted the scientific development of non-ART treatments, including those which seek to address underlying health conditions (Boyle et al., 2018). There is a pressing and critical need to develop robust registries of couples treated with non-ART treatments, for the improvement of outcomes and the promotion of robust consumer choice. (Spandorfer, 2020).
The ultimate measure of access to fertility care should be determined by the proportion of those with a desire for fertility who achieve a healthy live birth, whether or not ART is required to do so (Mascarenhas et al., 2012). Therefore, notwithstanding methodologic challenges, registry assessments should be developed and supported for all fertility treatments, not only ART.
Infertility affects \~20% of the couples in the world. Assisted reproductive technologies (ARTs) are currently the most common treatment option for infertility. Nevertheless, ARTs may be associated with complications for mothers and/or offspring. Natural procreative technology (NaProTechnology) is a natural treatment which minimizes these risks by seeking to identify the causes of infertility to enable better treatments. This narrative review summarizes the complications related to ARTs and clarifies how the NaProTechnology approach can help ARTs to achieve better results or be used in alternative to ARTs. Data in the literature indicate that NaProTechnology is a natural approach for treating infertility. The percentage of live births obtained by NaProTechnology is similar to that of ARTs. An extensive search for the genetic defects causing infertility or subfertility through genetic testing can help both ARTs and NaProTechnology to achieve successful pregnancies. By discovering the underlying causes of infertility, genetic tests enable better family counseling, like the implications of transmitting risk- and disease-alleles to future generations.
Del Giudice F et al., 2020·Fertility and sterility
To investigate the current evidence that correlates impaired male fertility with the risk of developing male-related malignancies. Systematic review and meta-analysis of population-based retrospective cohort studies. Not applicable. PATIENT(S): Men diagnosed with impaired fertility status and subsequently observed to determine incidence risk in developing testicular cancer (TCa) or prostate cancer (PCa). INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Pooled risk ratio (RR) differences among male factor infertility subjects compared with a fertile control population, and meta-regression analysis according to age at baseline, mean follow-up, range of study time, and year of publication. RESULT(S): Six studies met the inclusion criteria and were critically examined. Four studies examined male infertility and TCa (n = 161,634; 174 TCa cases), and four examined infertility in relation to PCa (n = 183,950 men; 377 PCa cases) from 1963 to 2014. The pooled RR was 2.033 (95% confidence interval [CI], 1.66-2.48); Q = 3.04 (degree of freedom [df] = 3); I2 = 1.55% for TCa and 1.68 (95% CI, 1.17-2.4); Q = 23.3(df = 3); I2 = 87.1% for PCa. CONCLUSION(S): Male infertility was associated with a subsequent risk of both TCa and PCa. Although the clinical significance of these findings remains uncertain, future studies should evaluate the underlying mechanisms to determine whether testis and prostate screening practices should be altered in men with male infertility. CLINICAL PROSPERO 167277.
General OB/GYNUK Regulatory FrameworkFertility Sector Oversight
Human Fertilisation and Embryology Authority, 2020
# State of the fertility sector 2019/2020
**Annual publication on our regulatory work**
November 2020
[**Download the underlying data set as.xlsx (47KB)**](https://www.hfea.gov.uk/media/3289/state-of-the-sector-2019-20-underlying-data.xlsx)
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### We are the independent regulator of fertility treatment and human embryo research in the United Kingdom (UK). We aim to ensure that everyone who steps into a fertility clinic, and everyone born as a result of treatment, receives high quality care. We do this by licensing, monitoring and inspecting fertility clinics and providing free, clear and impartial information about fertility treatment, clinics, and egg, sperm and embryo donation.
State of the Sector is our annual report, which summarises what we have seen through our regulatory work during the year. The report is compiled from information gathered from our inspections throughout the year and uses other sources of information including our Register of fertility treatments, incident reports and patient feedback mechanisms.
In 2019/20, we introduced a [**Clinical Governance Quarterly Update**](https://portal.hfea.gov.uk/knowledge-base/clinic-focus/) which provides clinics with detailed insight into non-compliances in a more timely manner to help clinics improve compliance and prepare for inspections. As a result, the State of the Sector report this year provides a high-level overview of sector-wide compliance, reporting on the absolute number of inspections, non-compliances, incidents and complaints.
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### Impact of COVID-19 This report looks at the financial year 2019/20 (1 April 2019 – 31 March 2020), predominantly covering the period before any COVID-19 restrictions were put in place. As COVID-19 caused unprecedented demand on the NHS during the initial wave of the pandemic, the Human Fertilisation and Embryology Authority (HFEA) made the difficult decision to publish [**General Direction 0014**](https://po...
Horodenchuk Z et al., 2020·Kwartalnik Naukowy Fides et Ratio
To assess the outcomes of treatment the couples with infertility or recurrent miscarriage with restorative reproductive approach and to identify predictors of success. It was a retrospective study of 282 married couples, who were included in the program in 2 outpatient gynaecological centers in May 2010 - December 2014. The couples were observed to the end of pregnancy (or pregnancies) or withdrawal from the program. All the couples were taught to track the cycle with the Creighton Model FertilityCare System or the sympto-thermal method, and almost all received additional medical treatment. The main outcome was live birth, the secondary outcomes included conceptions, unsuccessful pregnancies, low birth weight and prematurity. In life-table analysis, the adjusted cumulative proportion of first conceptions for those completing up to 24 months of NPT treatment was 77.7% (crude proportion 47.9%). The adjusted cumulative proportion of live births was 73.6% (117 births, crude proportion 41.5%). Mean time to achieving pregnancy was 8 months. All the births except one were singleton. There were only 3 preterm births. The favorable predictors of live birth were younger age, shorter time of trying for baby, good compliance, pregnancy in history. The unfavorable were hyperprolactinemia, uterine fibroids, endometriosis, male factor. The outcomes of restorative reproductive treatment the couples with infertility or recurrent miscarriage in Ukraine were comparable to those in Ireland and Canada.
We herein summarise the evidence concerning the impact of sperm DNA fragmentation in various clinical infertility scenarios and the advances on sperm DNA fragmentation tests. The collected evidence was used to formulate 41 recommendations. Of these, 13 recommendations concern technical aspects of sperm DNA fragmentation testing, including pre-analytical information, clinical thresholds and interpretation of results. The remaining 28 recommendations relate to indications for sperm DNA fragmentation testing and clinical management. Clinical scenarios like varicocele, unexplained infertility, idiopathic infertility, recurrent pregnancy loss, intrauterine insemination, in vitro fertilisation/intracytoplasmic sperm injection, fertility counselling for men with infertility risk factors and sperm cryopreservation have been contemplated. The bulk evidence supporting the recommendations has increased in recent years, but it is still of moderate to low quality. This guideline provides clinicians with advice on best practices in sperm DNA fragmentation testing. Also, recommendations are provided on possible management strategies to overcome infertility related to sperm DNA fragmentation, based on the best available evidence. Lastly, we identified gaps in knowledge and opportunities for research and elaborated a list of recommendations to stimulate further investigation.
The use of combined hormonal contraceptives (CHCs) worsens glucose tolerance, but the risk for glucose metabolism disorders remains controversial.
The study is a prospective longitudinal population-based cohort study. The study was based on a cohort population that comprised 1879 women born in 1966. At age 46, the women answered a questionnaire on contraceptive use and underwent an oral glucose tolerance test. Glucose metabolism indices were evaluated in current CHC (n = 153), progestin-only contraceptive (POC, n = 842), and non-hormonal contraceptive users (n = 884). In the entire study population, current CHC use was significantly associated with prediabetes (OR: 2.0, 95% CI: 1.3-3.2) and type 2 diabetes (OR: 3.3, 95% CI: 1.1-9.7) compared to non-hormonal contraceptive use. After 5 years of use, the prediabetes risk increased 2.2-fold (95% CI: 1.3-3.7) and type 2 diabetes risk increased 4.5-fold (95% CI: 1.5-13.5). Compared with the current POC use, current CHC use was significantly associated with prediabetes (OR: 1.9, 95% CI: 1.2-3.0). Current POC use was not associated with any glucose metabolism disorders. The results prevailed after adjusting for BMI and socioeconomic status. CHC use in perimenopausal women was associated with a significantly increased risk of glucose metabolism disorders. This association should be considered in women with increased metabolic risk.
Hormonal contraceptive drugs are being used by adult and adolescent women all over the world. Convergent evidence from animal research indicates that contraceptive substances can alter both structure and function of the brain, yet such effects are not part of the public discourse or clinical decision-making concerning these drugs. We thus conducted a systematic review of the neuroimaging literature to assess the current evidence of hormonal contraceptive influence on the human brain. The review was registered in PROSPERO and conducted in accordance with the PRISMA criteria for systematic reviews. Structural and functional neuroimaging studies concerning the use of hormonal contraceptives, indexed in Embase, PubMed and/or PsycINFO until February 2020 were included, following a comprehensive and systematic search based on predetermined selection criteria. A total of 33 articles met the inclusion criteria. Ten of these were structural studies, while 23 were functional investigations. Only one study investigated effects on an adolescent sample. The quality of the articles varied as many had methodological challenges as well as partially unfounded theoretical claims. However, most of the included neuroimaging studies found functional and/or structural brain changes associated with the use of hormonal contraceptives. The included studies identified structural and functional changes in areas involved in affective and cognitive processing, such as the amygdala, hippocampus, prefrontal cortex and cingulate gyrus. However, only one study reported primary research on a purely adolescent sample. Thus, there is a need for further investigation of the implications of these findings, especially with regard to adolescent girls.
Oral contraceptive use has been previously associated with an increased risk of suicidal behavior in some, but not all, samples. The use of large, representative, longitudinally-assessed samples may clarify the nature of this potential association. We used Swedish national registries to identify women born between 1991 and 1995 (N = 216 702) and determine whether they retrieved prescriptions for oral contraceptives. We used Cox proportional hazards models to test the association between contraceptive use and first observed suicidal event (suicide attempt or death) from age 15 until the end of follow-up in 2014 (maximum age 22.4). We adjusted for covariates, including mental illness and parental history of suicide. In a crude model, use of combination or progestin-only oral contraceptives was positively associated with suicidal behavior, with hazard ratios (HRs) of 1.73-2.78 after 1 month of use, and 1.25-1.82 after 1 year of use. Accounting for sociodemographic, parental, and psychiatric variables attenuated these associations, and risks declined with adjusted HRs ranged from 1.56 to 2.13 1 month beyond the initiation of use, and from 1.19 to 1.48 1 year after initiation of use. HRs were higher among women who ceased use during the observation period. Young women using oral contraceptives may be at increased risk of suicidal behavior, but risk declines with increased duration of use. Analysis of former users suggests that women susceptible to depression/anxiety are more likely to cease hormonal contraceptive use. Additional studies are necessary to determine whether the observed association is attributable to a causal mechanism.
Long acting reversible contraceptives (LARC), including intrauterine devices (IUDs) and contraceptive implants, can support an individual in meeting their reproductive goals by allowing them to prevent pregnancy effectively. These devices can also limit an individual's control over reproduction because they generally require an in-person visit to a health care provider for removal. Returning for another visit may be logistically challenging for many individuals who may need to arrange for transportation, childcare, or take time off from work. Effectively negotiating with a provider to request removal may be additionally challenging for medically underserved and disenfranchised people who may not feel empowered to do so. The objective of this study was to assess providers' willingness to honor patients' requests for IUD and contraceptive implant removal on the day of the request. A survey was conducted in which clinicians were presented with scenarios of women requesting IUD or implant removal. Clinicians were asked what they were most likely to do. A total of 105 clinicians were surveyed. The responses of 60 clinicians who inserted IUDs and 57 who provided the contraceptive implant were included in the analysis. When asked about same-day removal of an IUD or implant from a dissatisfied patient who requested removal, 40% stated they would remove the implant, and 57% stated they would remove the IUD on the day of the request. Findings from this study suggest many clinicians would be unwilling or unable to accommodate a patient's request for device removal at the time of their visit. This delay or refusal represents a significant barrier for patients and has implications for reproductive autonomy that should be further explored.
Perimenopause/MenopauseDHEA SupplementationHormonal TreatmentDehydroepiandrosterone
Open Access
Dehydroepiandrosterone (DHEA) concentration decreases with age, therefore, DHEA has been considered a hormone that reduces the symptoms associated with aging, so the usefulness of DHEA in premenopausal and postmenopausal women, and the options of hormone therapy have received a large amount of attention. The effectiveness of DHEA in the premenopausal women remains unclear, while in postmenopausal women with coexisting estrogens deficiency is controversial. Despite many years of study, the use of DHEA is still controversial, especially regarding its effectiveness. The aim of present article was to evaluate DHEA specific effects on metabolic parameters, bone mineral density, insulin resistance as well as the therapeutic potential of DHEA in preand postmenopausal women using measures of sexual activity, cognition and well-being. The summary of this article is the position statement of expert group of the Polish Menopause and Andropause Society regarding the efficacy and safety of DHEA supplementation in women. We concluded, that currently available clinical trials and meta-analyses indicate that DHEA supplementation is effective in women with adrenal insufficiency and chronically treated with exogenous glucocorticoids, postmenopausal women with low bone mineral density and/or osteoporosis, premenopausal women with sexual disorders and low libido, and in women with vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause. Currently available clinical trials also suggest that DHEA supplementation is probably effective in postmenopausal women with hypoactive sexual disorders, infertile women with diminished ovarian reserve, women suffering from depression and anxiety, and women with obesity and insulin resistance. No serious adverse effects have been reported.
In this Commentary, we explain the case for a standardized cesarean delivery surgical technique. There are three strong arguments for a standardized approach to cesarean delivery, the most common major abdominal surgery performed in the world. First, standardization within institutions improves safety, efficiency, and effectiveness in health care delivery. Second, surgical training among obstetrics and gynecology residents would become more consistent across hospitals and regions, and proficiency in performing cesarean delivery measurable. Finally, standardization would strengthen future trials of cesarean delivery technique by minimizing the potential for aspects of the surgery which are not being studied to bias results. Before 2013, more than 155 randomized controlled trials, meta-analyses or systematic reviews were published comparing various aspects of cesarean delivery surgical technique. Since 2013, an additional 216 similar studies have strengthened those recommendations and offered evidence to recommend additional cesarean delivery techniques. However, this amount of cesarean delivery technique data creates a forest for the trees problem, making it difficult for a clinician to synthesize this volume of data. In response to this difficulty, we propose a comprehensive, evidence-based and standardized approach to cesarean delivery technique.
Wang JW et al., 2020·Therapeutic Advances in Reproductive Health
Previous studies show good technical success rates for fallopian tube recanalization. Scarce literature exists regarding advance techniques currently used by interventional radiologists during fallopian tube recanalization procedures. This study investigates the level of intervention and tubal patency and its association with technical success and associated pregnancy outcomes. We retrospectively evaluated fallopian tube recanalization procedures performed at a single center in a 24-year period. A total of 160 couples undergoing a basic infertility evaluation were included. Hysterosalpingography with high pressure contrast injection followed by selective contrast, guidewire catheterization at the tubal ostium, and/or microcatheter/microwire recanalization were performed. Comparisons of the tubal fertilization rate by relevant characteristics were tested for statistical significance with t tests for continuous data or with Pearson chi-square tests for categorical data. Technical success rate was 94% (319 of 341 tubes). High pressure contrast injection alone (184 of 341, 54%), selective catheterization (40%), and microcatheter/microwire (6%) interventions yielded technical success rates of 98%, 90%, and 73%, respectively. The overall rate of conception was 35% (17 of 48). Current techniques of fallopian tube recanalization offer a desirable and safe option with high technical success for patients seeking treatment for infertility due to proximal fallopian tube obstruction.
To consolidate evidence from systematic reviews and meta-analyses investigating the association between reproductive factors in women of reproductive age and their subsequent risk of cardiovascular disease. Umbrella review. Medline, Embase, and Cochrane databases for systematic reviews and meta-analyses from inception until 31 August 2019. Two independent reviewers undertook screening, data extraction, and quality appraisal. The population was women of reproductive age. Exposures were fertility related factors and adverse pregnancy outcomes. Outcome was cardiovascular diseases in women, including ischaemic heart disease, heart failure, peripheral arterial disease, and stroke. 32 reviews were included, evaluating multiple risk factors over an average follow-up period of 7-10 years. All except three reviews were of moderate quality. A narrative evidence synthesis with forest plots and tabular presentations was performed. Associations for composite twofold for pre-eclampsia, stillbirth, and preterm birth; 1.5-1.9-fold for gestational hypertension, placental abruption, gestational diabetes, and premature ovarian insufficiency; and less than 1.5-fold for early menarche, polycystic ovary syndrome, ever parity, and early menopause. A longer length of breastfeeding was associated with a reduced risk of cardiovascular disease. The associations for ischaemic heart disease were twofold or greater for pre-eclampsia, recurrent pre-eclampsia, gestational diabetes, and preterm birth; 1.5-1.9-fold for current use of combined oral contraceptives (oestrogen and progesterone), recurrent miscarriage, premature ovarian insufficiency, and early menopause; and less than 1.5-fold for miscarriage, polycystic ovary syndrome, and menopausal symptoms. For stroke outcomes, the associations were twofold or more for current use of any oral contraceptive (combined oral contraceptives or progesterone only pill), pre-eclampsia, and recurrent pre-eclampsia; 1.5-1.9-fold for current use of combined oral contraceptives, gestational diabetes, and preterm birth; and less than 1.5-fold for polycystic ovary syndrome. The association for heart failure was fourfold for pre-eclampsia. No association was found between cardiovascular disease outcomes and current use of progesterone only contraceptives, use of non-oral hormonal contraceptive agents, or fertility treatment. From menarche to menopause, reproductive factors were associated with cardiovascular disease in women. In this review, presenting absolute numbers on the scale of the problem was not feasible; however, if these associations are causal, they could account for a large proportion of unexplained risk of cardiovascular disease in women, and the risk might be modifiable. Identifying reproductive risk factors at an early stage in the life of women might facilitate the initiation of strategies to modify potential risks. Policy makers should consider incorporating reproductive risk factors as part of the assessment of cardiovascular risk in clinical guidelines. PROSPERO CRD42019120076.
Per- and polyfluoroalkyl substances (PFASs) are used in specialty/functional textiles to impart oil, water, and stain repellency. Little is known, however, with regard to the occurrence of PFASs in textiles including infant clothing. In this study, 13 perfluoroalkyl acids (PFAAs), comprising four perfluoroalkyl sulfonic acids (PFSAs; C4-C10) and nine perfluoroalkyl carboxylic acids (PFCAs; C4-C12) were determined in 160 textile samples collected from the United States. Two extraction methods, one involving a simple solvent extraction (i.e., before oxidation) and the other with an oxidative treatment (i.e., after oxidation) of textile extracts, were used. The sum concentrations of 13 PFAAs (i.e., ∑PFAA) in textile extracts before oxidation ranged from 2 (2 (14.2 ng/g). ∑PFAA concentrations were the highest in flame retarded textiles (n = 23; 13.3 μg/m2; 59.4 ng/g), followed by water repellent textiles (n = 56; 2.88 μg/m2; 12.9 ng/g) and infant clothes (n = 81; 0.521 μg/m2; 2.33 ng/g). C4-C10 PFCAs accounted for at least three-quarters of the ∑PFAA content in our textile samples. Textile extracts analyzed after oxidative treatment exhibited ∑PFAA concentrations 10-fold higher than those in extracts analyzed prior to oxidation, which suggested that PFAA precursors are used in textiles. Precursors that generated C4-C5 PFCAs, upon oxidation, were more prevalent than those that yielded PFOA. The calculated dermal exposure doses in infants of PFAAs present in clothes were at least 1-2 orders of magnitude below the reference doses proposed by the United States Environmental Protection Agency. This is the first time that the oxidative treatment was applied in the analysis of PFASs in textiles, and our results suggest the existence of PFCA precursors in textiles.