Effects of SARS-COV-2 infection during the frozen-thawed embryo transfer cycle on embryo implantation and pregnancy outcomes.

STUDY QUESTION: Does severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the frozen-thawed embryo transfer (FET) cycle affect embryo implantation and pregnancy rates? SUMMARY ANSWER: There is no evidence that SARS-CoV-2 infection of women during the FET cycle negatively affects embryo implantation and pregnancy rates. WHAT IS KNOWN ALREADY: Coronavirus disease 2019 (COVID-19), as a multi-systemic disease, poses a threat to reproductive health. However, the effects of SARS-CoV-2 infection on embryo implantation and pregnancy following fertility treatments, particularly FET, remain largely unknown. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study, included women who underwent FET cycles between 1 November 2022 and 31 December 2022 at an academic fertility centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who tested positive for SARS-CoV-2 during their FET cycles were included in the COVID-19 group, while those who tested negative during the same study period were included in the non-COVID-19 group. The primary outcome was ongoing pregnancy rate. Secondary outcomes included rates of implantation, biochemical pregnancy, clinical pregnancy, early pregnancy loss, and ongoing pregnancy. Multivariate logistic regression models were applied to adjust for potential confounders including age, body mass index, gravidity, vaccination status, and endometrial preparation regimen. Subgroup analyses were conducted by time of infection with respect to transfer (prior to transfer, 1-7 days after transfer, or 8-14 days after transfer) and by level of fever (no fever, fever <39°C, or fever ≥39°C). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 243 and 305 women were included in the COVID-19 and non-COVID-19 group, respectively. The rates of biochemical pregnancy (58.8% vs 62.0%, P = 0.46), clinical pregnancy (53.1% vs 54.4%, P = 0.76), implantation (46.4% vs 46.2%, P = 0.95), early pregnancy loss (24.5% vs 26.5%, P = 0.68), and ongoing pregnancy (44.4% vs 45.6%, P = 0.79) were all comparable between groups with or without infection. Results of logistic regression models, both before and after adjustment, revealed no associations between SARS-CoV-2 infection and rates of biochemical pregnancy, clinical pregnancy, early pregnancy loss, or ongoing pregnancy. Moreover, neither the time of infection with respect to transfer (prior to transfer, 1-7 days after transfer, or 8-14 days after transfer) nor the level of fever (no fever, fever <39°C, or fever ≥39°C) was found to be related to pregnancy rates. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study is subject to possible selection bias. Additionally, although the sample size was relatively large for the COVID-19 group, the sample sizes for certain subgroups were relatively small and lacked adequate power, so these results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The study findings suggest that SARS-CoV-2 infection during the FET cycle in females does not affect embryo implantation and pregnancy rates including biochemical pregnancy, clinical pregnancy, early pregnancy loss, and ongoing pregnancy, indicating that cycle cancellation due to SARS-CoV-2 infection may not be necessary. Further studies are warranted to verify these findings. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2023YFC2705500, 2019YFA0802604), National Natural Science Foundation of China (82130046, 82101747), Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210201, SHSMU-ZLCX20210200, SSMU-ZLCX20180401), Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003), Science and Technology Commission of Shanghai Municipality (23Y11901400), Shanghai Sailing Program (21YF1425000), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36), and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161413). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Effectiveness of Manual Hysteroscopic Tissue Removal Device for Intrauterine Polyps in Infertile Women in Both Operating and Office Settings.

Background: Mechanical hysteroscopic tissue removal (mHTR) systems are widely used for removing intrauterine pathology. Given the startup and procedural costs for electrically powered mechanical units, disposable manual mHTR systems have been developed. Methods: With little published, we describe its effectiveness for hysteroscopic intrauterine polypectomy. Results: One-hundred fifty-seven infertile women underwent hysteroscopic polypectomy with the manual mHTR device. Complete removal was accomplished in all but three cases, with blood loss being <10 mL and all specimens deemed sufficient for histopathologic diagnosis. Conclusions: These results suggest that the disposable manual mHTR system is effective in removing endometrial polyps. Head-to-head comparisons with other alternative technologies are needed.

Psychosocial outcomes of children born via embryo donation.

STUDY QUESTION: What are parents' perceptions of their relationships with and the psychosocial adjustments of their children who are born via embryo donation? SUMMARY ANSWER: Families created through embryo donation have well-adjusted parent-child relationships and reassuring child psychosocial outcomes. WHAT IS KNOWN ALREADY: Embryo donation is an effective and growing form of third-party reproduction, but there is limited research in this field. Prior studies suggest that families created through gamete donation function well regarding parent-child relationship quality and child behavioral and socioemotional adjustment. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional survey study with 187 total participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: Parents of children born via embryo donation were recruited nationally by contacting all embryo donation programs registered with the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) as well as medically directed embryo donation or 'embryo adoption' centers. Participants completed three online Qualtrics questionnaires. The first was a survey including 33 questions on demographics, the procurement process, and self-reported obstetric outcomes. Participants also completed two standardized measures assessing children's behavior and parents' adjustment to parenthood: the Strengths and Difficulties Questionnaire (SDQ) and the Parental Acceptance-Rejection Questionnaire (PARQ). Scoring of the SDQ and PARQ was totaled and compared to standardized values (SDQ) or previously published results on other forms of gamete donation (PARQ), such as oocyte donation and sperm donation. MAIN RESULTS AND THE ROLE OF CHANCE: On the SDQ (n = 46), the average total difficulties scores by age were: 8.2 ± 0.98 for ages 2-4, 7.6 ± 0.93 for ages 5-10, and 3.5 ± 0.77 for ages 11-17; this is compared to the normal reported range of 0-13, which indicates that clinically significant psychosocial problems are unlikely. Across all ages and individual categories (emotional symptoms, conduct problem, hyperactivity, peer problem, prosocial), scores on the SDQ were within the normal ranges. The average PARQ score (n = 70) for all respondents was 27.5 ± 1.18 (range: 24-96), suggesting perceived parental acceptance. LIMITATIONS, REASONS FOR CAUTION: Because this study was cross-sectional, it could not capture familial relationships over time. This survey-based study design allows for potential selection bias (parents of well-adjusted children may be more likely to participate). Additionally, the overall sample size is relatively small; however, it remains one of the largest published to date. Another significant limitation to this study is the lack of generalizability: most participants were recruited from private, faith-based, embryo donation programs who are demographically similar. WIDER IMPLICATIONS OF THE FINDINGS: Though embryo donation is an established form of third-party reproduction, it is significantly less robustly studied compared to other forms of gamete donation (oocyte or sperm donation). This study provides a larger data set with a more expanded age range of children compared to the limited number of previously published studies. Furthermore, these findings indicate a high parental disclosure rate with respect to the use of embryo donation which contrasts previous findings. STUDY FUNDING/COMPETING INTEREST(S): No external funding source was utilized for the completion of this study. No conflicts are disclosed. TRIAL REGISTRATION NUMBER: N/A.

Total and bioavailable 25-hydroxyvitamin D is not associated with improved sexual dysfunction following vitamin D supplementation in women with polycystic ovarian syndrome: a pilot study.

BACKGROUND: Vitamin D (Vit D) deficiency has been linked to symptoms of polycystic ovary syndrome (PCOS), yet little is known about Vit D supplementation as a treatment for sexual dysfunction (SDy) in women with PCOS. AIM: To explore the implications of serum total 25-hydroxyvitamin D (25[OH]D) and bioavailable 25[OH]D (bio-25[OH]D) status and replacement on women with PCOS and SDy. METHODS: Reproductive-age women with PCOS who were not desiring fertility were eligible provided that they also had SDy, as assessed by the Female Sexual Function Index (FSFI), and were without severe depression, as evaluated by the Beck Depression Inventory II (BDI-II). Participants were given the recommended dietary allowance of Vit D (600 IU daily) plus hormonal contraception (HC; cyclic ethinyl estradiol/drospirenone) or no HC for 6 months. Comparisons between groups were analyzed by chi-square test and t-test, and Pearson's correlation coefficient analyzed correlations between FSFI with demographics, BDI-II, androgen levels, and total and bio-25[OH]D. OUTCOMES: The outcomes included SDy (FSFI <26.55), total and serum bio-25[OH]D levels, and total and free testosterone. RESULTS: A total of 42 women without severe depression completed the FSFI, with 28 (66.7%) having SDy. All FSFI domains, including arousal, lubrication, orgasm, and pain, were significantly lower as compared with women without SDy, with no associations with respect to demographics, total and free testosterone, or total and bio-25[OH]D. Vit D replacement was initiated with HC (n = 18) or no HC (n = 10), and for those completing the study, FSFI improved (score >26.55) in 61% (11/18) regardless of the treatment group. A time-treatment effect showed a significant change for the domain of orgasm, suggesting that HC had more of an impact than Vit D replacement. Improvement in sexual function as a dichotomous variable was not associated with age, body mass index, other demographics, total and free testosterone, total and bio-25[OH]D, or HC use. CLINICAL IMPLICATIONS: Due to the prevalence of SDy in women with PCOS, efficacious treatment options are necessary. STRENGTHS AND LIMITATIONS: This study is the first to analyze the effect of Vit D supplementation on SDy in women with PCOS. Limitations included the small number of participants who completed the study, thus limiting meaningful conclusions and generalizability. CONCLUSION: Vit D status was not associated with SDy and BDI-II. While HC may have played a role, standard Vit D supplementation could not account for the noted improvement in FSFI in women with PCOS.

Benefits of Blastocyst Transfer With at Least Three Good-Quality Cleavage-stage Embryos in Women of Advanced Maternal Age: A Retrospective Analysis.

OBJECTIVES: Limited studies on the benefits of blastocyst transfer in advanced maternal age (AMA) (≥40 years) have been reported. Our objective was to find whether blastocyst-stage embryo transfer improves pregnancy and live birth rates in women ≥40 years who have 3 or more good-quality cleavage-stage embryos. METHODS: All fresh in vitro fertilization-intracytoplasmic sperm injection cycles performed from January 2020 to December 2021 in AMA women that progressed to transfer were considered for analysis. We compared fresh and cumulative ongoing pregnancy rates in AMA women of those who had a cleavage-stage transfer, while meeting the criteria for extended culture (≥3 high-quality embryos, group 1), and those who underwent blastocyst transfer (group 2). Demographic parameters, stimulation, embryology, fresh and cumulative ongoing pregnancy rates, and clinical miscarriage rates were compared. RESULTS: During the study period, 255 cycles were analyzed including group 1 (n = 99) and group 2 (n = 156). Group 1 participants were older and had a greater number of embryos for transfer. Fresh and cumulative ongoing pregnancy rates per transfer were higher in group 2 compared to group 1 (23.4% vs. 13.1%, P = 0.04; 25.5% vs. 14.1%, P = 0.03), while overall miscarriage rates were higher in group 1 than group 2 (51.7% vs. 25%, P = 0.01). CONCLUSIONS: Blastocyst culture provides a benefit to AMA women who have at least 3 good-quality embryos on day 3 resulting in significantly higher fresh and cumulative ongoing pregnancy rates and lower miscarriage compared to cleavage-stage transfers.

Anti-Müllerian hormone levels are associated with skeletal maturity in adolescent girls in the Fels Longitudinal Study.

The role of anti-Müllerian hormone (AMH), a potential marker of the hypothalamic-pituitary-ovarian axis, is not well established in adolescent females. Most studies use secondary sexual characteristics or chronological age as predictors for AMH. Skeletal maturity, an indicator of bone development, has not been examined to predict AMH. This study sought to examine patterns of change in AMH in relation to skeletal maturity. Demographics, anthropometry, hand-wrist radiographs, and cardiometabolic risk factors from 88 females (212 observations), between the ages of 8 to 18 years from the Fels Longitudinal Study were used in this study. AMH was analyzed using ELISA from stored frozen serum samples. Generalized linear mixed effect modeling was used. In the stepwise regression models, log-transformed AMH (AMHlog) was regressed on relative skeletal age as the skeletal maturity indicator (calculated as chronological age minus skeletal age) and adjusted for chronological age, adiposity, and cardiometabolic risk factors. Skeletal maturity significantly predicted lower AMHlog (ß= -0.073, SE=0.032, p=0.023). Glucose was significantly associated with decreases in AMHlog (ß= -0.008, SE=0.004, p=0.044). Chronological age modeled as a cubic function was not significant. AMH and skeletal maturity may provide correlated information on growth and pubertal status in adolescent females.

Use of the Free Endometriosis Risk Advisor App as a Non-Invasive Screening Test for Endometriosis in Patients with Chronic Pelvic Pain and/or Unexplained Infertility.

Endometriosis is a prevalent condition that affects millions of individuals globally, leading to various symptoms and significant disruptions to their quality of life. However, the diagnosis of endometriosis often encounters delays, emphasizing the pressing need for non-invasive screening. This retrospective cross-sectional study aimed to evaluate the utility of the Endometriosis Risk Advisor (EndoRA) mobile application in screening for endometriosis in patients with chronic pelvic pain and/or unexplained infertility. The study consisted of 293 patients who met specific criteria: they were English-speaking individuals with chronic pelvic pain and/or unexplained infertility, owned smartphones, and had no prior diagnosis of endometriosis. The results demonstrated that the EndoRA score exhibited a high sensitivity of 93.1% but a low specificity of 5.9% in detecting endometriosis. The positive predictive value was 94.1%, while the negative predictive value was 5.0%. Although the study had limitations and potential selection bias, its findings suggest that EndoRA can serve as a valuable screening tool for high-risk individuals, enabling them to identify themselves as being at an increased risk for endometriosis. EndoRA's non-invasive nature, free access, and easy accessibility have the potential to streamline evaluation and treatment processes, thereby empowering individuals to seek timely care and ultimately improving patient outcomes and overall well-being.

Fertility and Sterility top videos from 2021.

OBJECTIVE: To objectively grade all video publications in Fertility and Sterility during the year 2021 and compile a list of the top 10 surgical videos. DESIGN: A descriptive presentation of the 10 highest-scoring video publications from Fertility and Sterility in the year 2021. SETTING: Not applicable. PATIENT/ANIMALS: Not applicable. INTERVENTIONS: J.F., Z.K., J.P.P., and S.R.L. acted as independent reviewers of all video publications. A standardized scoring method was used to score all videos. MAIN OUTCOME MEASURES: Up to 5 points were awarded for each of the following categories: scientific merit or clinical relevance of the topic; clarity of the video; use of an innovative surgical technique; and video editing or the use of marking tools on the video to highlight important features or surgical landmarks. This allowed a maximum score of 20 for each video. The number of YouTube views and likes was used as a tiebreaker if ≥2 videos scored similarly. The interclass coefficient from a 2-way random effects model was calculated to assess the agreement among the 4 independent reviewers. RESULT(S): A total of 36 videos were published in Fertility and Sterility during the year 2021. After averaging scores from all 4 reviewers, a top-10 list was created. The overall interclass correlation coefficient for the 4 reviews was 0.89 (95% confidence interval, 0.89-0.94). CONCLUSION(S): An overall substantial agreement was noted among the 4 reviewers. A total of 10 videos reigned supreme from a list of very competitive publications that had already undergone the peer review process. The subject matter of these videos ranged from complex surgical procedures, including uterine transplantation, to common procedures, such as GYN ultrasound.

Disposition of unused cryopreserved embryos: opportunities and liabilities.

Cryopreservation of embryos has become an essential aspect of assisted reproductive technology, allowing for greater clinical efficiency and increased safety. However, the increasing numbers of cryopreserved embryos in clinics worldwide pose challenges to all stakeholders with respect to the disposition and donation of one's embryos when the gamete providers have completed their family building. The following series of articles provides an update of outcomes, challenges, and controversies related to embryo disposition. The first article describes the current and future medical potential of donated embryos for human stem cell research and other applications. Second, the practice of embryo donation to other intended parent(s) is summarized, and a review of the literature on child outcomes is presented. Third, the logistics and programmatic steps in managing embryos designated for disposal are discussed, including the option for compassionate transfer. Fourth, legal experts summarize precedent setting cases in the United States and the current legal environment of unused embryo management in the setting of the recent Supreme Court decision in Dobbs v. Jackson Women's Health Organization.

Comparing pregnancy rates following ovarian stimulation with follitropin-Δ to follitropin -α in routine IVF: A retrospective analysis.

STUDY OBJECTIVES: Follitropin-Δ, a new recombinant follicle stimulation hormone, uses a fixed daily dose producing a predictable ovarian response while using less gonadotropins compared to follitropin-α. We report clinical outcomes comparing each in the routine IVF setting and further compare qualified to disqualified subjects based on previous randomized controlled trial (RCT) inclusion criteria. STUDY DESIGN: Retrospective analysis of all cycles performed by a single provider between January 2020 to January 2021. All IVF cycles without patient inclusion-exclusion criteria were considered for the analysis. Clinical outcomes in two groups (follitropin-Δ vs follitropin-α ± 75 IU human menopausal gonadotropin (hMG) in expected poor responders) were compared. In addition, comparisons were made between qualified versus disqualified subgroups. RESULTS: No differences in baseline demographics, number of MII oocytes, fertilization/MII oocyte, percent of good quality embryos were noted. Compared to those using follitropin-α, follitropin-Δ resulted in lower daily (170 vs 211 IU/d, p = 0.002) and total Gn used (1739 vs 2194 IU, p = 0.003). Optimal range response (8-14 oocytes) (22/44 [50 %] vs 78/203 [38.6 %]; p = 0.10) and fresh (fCP) and cumulative clinical pregnancy (cCP) rates per transfer (29.5 % vs 24.1 % and 35 % vs 25.1 %, p = 0.08) were similar between groups. Based on previous RCTs, those who would have qualified compared to those who would have disqualified, patients using follitropin-Δ were just as likely to have an optimal oocyte response (qualified: 48 % vs disqualified: 57.1 %) and resulted in similar cCP (41.4 % vs 25 %, p-0.23). CONCLUSIONS: While follitropin-Δ requires less daily and total dosing compared to follitropin-α, optimal range of retrieved oocytes and clinical outcomes appear to be comparable. Using RCT inclusion criteria, similar findings were noted in those who would have qualified compared to disqualified patients.