Ovulation-induced frozen embryo transfer regimens in women with polycystic ovary syndrome: a systematic review and meta-analysis.

PURPOSE: To evaluate whether the type of frozen embryo transfer (FET) regimen - ovulation-induced regimens vs. hormone replacement therapy regimens (HRT) - is associated with live birth rates and the risk of hypertensive diseases of pregnancy (HDP) in women with polycystic ovary syndrome (PCOS). METHODS: All studies in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched using a combination of MeSH terms and keywords. Inclusion criteria included studies on women with a diagnosis of PCOS, utilization of FET, and reporting of pregnancy and/or obstetric outcomes. Studies were excluded if they were case series or conference abstracts or used other FET regimens. A random effects meta-analysis was performed. Primary outcomes include relative risk (RR) of live birth and HDP. RESULTS: Eleven studies were included in the meta-analysis for the final review. Ovulation-induced regimens were associated with a higher live birth rate (8 studies, RR 1.14 [95% CI 1.08, 1.21]) compared to HRT regimens. The risk of HDP (3 studies RR 0.78 [95% CI 0.53, 1.15]) was not significantly different. Ovulation-induced regimens were associated with a lower miscarriage rate (9 studies, RR 0.67 [95% CI 0.59-0.76]). Rates of clinical pregnancy (10 studies, RR 1.05 [95% CI 0.99, 1.11]) and ectopic pregnancy (7 studies, RR 1.40 [95% CI 0.84, 2.33]), were not significantly different. CONCLUSION: This SR/MA demonstrates that for women with PCOS, ovulation-induced FET regimens are associated with higher rates of live birth and lower rates of miscarriage compared to HRT regimens.

Resolution of Hyperandrogenism, Insulin Resistance and Acanthosis Nigricans (HAIR-AN) Syndrome After Sleeve Gastrectomy.

Hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN) is a severe subphenotype of polycystic ovary syndrome (PCOS). A 32-year-old woman with HAIR-AN and class 3 obesity presented to an endocrinology clinic after she failed sequential trials of treatment with metformin, estrogen-progestin OCP, spironolactone, leuprolide, and a levonorgestrel intrauterine device. She complained of hirsutism and acanthosis nigricans severely affecting her quality of life and had secondary amenorrhea. Laboratory evaluation showed extremely elevated testosterone and insulin levels and elevated glycated hemoglobin A1c (HbA1c). She underwent laparoscopic sleeve gastrectomy. One year after the surgery, she lost 32% of her body weight and reported normalization of menses, dramatic improvement in hirsutism, and near-resolution of acanthosis nigricans. Her testosterone, insulin, and HbA1c normalized. This case demonstrates the central role of hyperinsulinemia in HAIR-AN and suggests that aggressive measures to normalize insulin resistance and reduce excess weight can effectively treat the reproductive abnormalities in this syndrome. We suggest that bariatric surgery can be an effective cure for HAIR-AN syndrome and that PCOS, including HAIR-AN, should be considered a comorbidity of obesity during evaluation of bariatric surgery candidates.

Weight Bias in Reproductive Medicine: A Curiously Unexplored Frontier.

Obesity has been associated with a multitude of medical comorbidities, infertility, and adverse obstetric outcomes. Weight stigma and weight bias pervade not only the medical field but also education, employment, and activities of daily living. The experience of weight stigma has been shown to adversely impact not only the mental health of individuals with overweight or obesity but also worsen obesogenic behaviors, and medical comorbidities. This review frames the rise of weight stigma and weight bias within the context of the "obesity epidemic" and explores its associations with infertility and decreased access to health care and its subsequent impact on the lives of individuals. Furthermore, it explores the concepts of intrinsic and extrinsic weight stigma/bias and highlights the need for further examination and research into the impact of these factors on access to reproductive medicine and subsequent outcomes.

Moderate and increased physical activity is not detrimental to live birth rates among women with unexplained infertility and obesity.

Objective: To determine if moderate physical activity is associated with live birth rates in women with unexplained infertility and obesity. Design: Secondary analysis of the Improving Reproductive Fitness through Pretreatment with Lifestyle Modification in Obese Women with Unexplained Infertility trial. Setting: US fertility centers, 2015-2019. Patients: A total of 379 women participated in Improving Reproductive Fitness through Pretreatment with Lifestyle Modification in Obese Women with Unexplained Infertility trial, a lifestyle modification program with increased physical activity (phase I, 16 weeks) and up to three cycles of clomiphene citrate treatment and intrauterine insemination (phase II). Interventions: Participants were instructed to add 500 steps/day weekly until a maximum of 10,000 steps/day was reached and maintained. Participants were stratified as active (top third, N = 125) and less active (lower third, N = 125) on the basis of the average number of steps per day recorded using a FitBit activity tracker. Main Outcome Measures: Live birth rate. Results: Active participants were more physically active at the time of enrollment than less active participants (average baseline steps per day, 8,708 [7,079-10,000] vs. 4,695 [3,844-5,811]; P ≤ 0.001) and were more likely to reach 10,000 steps/day than less active participants (average steps per day, 10,526 [9,481-11,810] vs. 6,442 [4,644-7,747]; P ≤ 0.001), although both groups increased their average steps per day by a similar amount (1,818 vs.1,747; P = 0.57). There was no difference in live birth rates (24/125 [19.2%] vs. 25/125 [20%]; P = 0.87) between active and less active participants nor were there differences in clinical pregnancy rates (P = 0.45) or miscarriage rates (P = 0.49) between the two groups. Conclusions: Active participants were more likely to achieve the physical activity goal, although this was not associated with benefit or harm with respect to live birth. Clinical Trial Registration Number: ClinicalTrials.gov (NCT02432209), first posted: May 4, 2015.

Preconception health optimization in women with polycystic ovary syndrome - how to find the time?

PURPOSE OF REVIEW: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, the most common cause of infertility among women and a major contributor to pregnancy complications. RECENT FINDINGS: Diagnostic and associated features of PCOS, including hyperandrogenism, insulin resistance, and obesity, contribute to the 2-4-fold increased risk of pregnancy-induced hypertension and preeclampsia, gestational diabetes and preterm birth observed among pregnant women with PCOS. PCOS should be diagnosed according to the 2018 International Guideline. Screening for and optimizing management of hypertension, impaired glucose tolerance and obesity in the preconception window in women with PCOS provides an opportunity to increase the odds of a spontaneous pregnancy, live birth with fertility treatment and possibly reduce the risk of pregnancy complications. SUMMARY: Providers should prioritize individualizing recommendations for preconception health optimization in women with PCOS in order to maximize the chance of conception, a healthy pregnancy and the health of future generations.

Worth the wait? Preconception weight reduction in women and men with obesity and infertility: a narrative review.

Short and long-term weight reduction interventions are considered in the preconception period for women and men with obesity and infertility as obesity is associated with poorer reproductive outcomes. Short-term weight loss achieved with diet, exercise, and medications does not improve per cycle conception or live birth rates in women undergoing ovulation induction, intrauterine insemination, or in vitro fertilization (IVF), but may increase the rate of natural conception. Long-term weight loss achieved through surgical interventions may increase spontaneous conceptions, particularly among women with polycystic ovary syndrome, and may increase the live birth rate from IVF, though these findings are limited by recent evidence. There is a clear need for additional treatment options and well-designed weight loss intervention trials that address the heterogeneous causes of obesity among women and men with infertility and include fertility outcomes and perinatal morbidity as outcome measures.

Virtual Compared With In-Clinic Transvaginal Ultrasonography for Ovarian Reserve Assessment.

OBJECTIVE: To evaluate noninferiority of virtual transvaginal ultrasonography compared with in-clinic ultrasonography for ovarian reserve assessment. METHODS: We conducted a single-site, head-to-head crossover trial. Participants performed self-administered virtual transvaginal ultrasonography at home, guided by a remote-certified ultrasound technologist, then underwent transvaginal ultrasonography in-clinic with another ultrasound technologist. Participants were women in the greater Boston area interested in evaluating ovarian reserve and recruited through social media, health care referrals, and professional networks. The uterus and ovaries were captured in sagittal and transverse views. These randomized recordings were reviewed by two or three independent, blinded reproductive endocrinologists. The primary outcome was noninferiority of the rate of clinical quality imaging produced at home compared with in clinic. Sample size was selected for greater than 90% power, given the 18% noninferiority margin. Secondary outcomes included antral follicle count equivalency and net promoter score superiority. RESULTS: Fifty-six women were enrolled from December 2020 to May 2021. Participants varied in age (19-35 years), BMI (19.5-33.9), and occupation. Ninety-six percent of virtual and 98% of in-clinic images met "clinical quality." The difference of -2.4% (97.5% CI lower bound -5.5%) was within the noninferiority margin (18%). Antral follicle counts were equivalent across settings, with a difference in follicles (0.23, 95% CI -0.36 to 0.82) within the equivalence margin (2.65). Virtual examinations had superior net promoter scores (58.1 points, 97.5% CI of difference 37.3-79.0, P<.01), indicating greater satisfaction with the virtual experience. CONCLUSION: Virtual transvaginal ultrasonography remotely guided by an ultrasonography technologist is noninferior to in-clinic transvaginal ultrasonography for producing clinical quality images and is equivalent for estimating antral follicle count. Virtual transvaginal ultrasonography had superior patient satisfaction and has potential to significantly expand patient access to fertility care. FUNDING SOURCE: This study was sponsored by Turtle Health. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04687189.

Fertility, Contraception, and Novel Reproductive Technologies in Chronic Kidney Disease.

Chronic kidney disease (CKD) affects hypothalamic-pituitary-gonadal axis function, leading to menstrual abnormalities, sexual dysfunction, functional menopause, and loss of fertility. Pregnancy in a patient with CKD is associated with a higher risk of complications to both the mother and the fetus, highlighting the importance of contraceptive counseling at all stages of CKD. There has been limited research on the safety and efficacy of different contraceptive methods in the CKD population, and it is important to tailor the choice of contraception to the patient's lifestyle and comorbidity status. Cyclophosphamide is a commonly used immunosuppressive agent that impairs fertility in a dose-dependent fashion, with greater impact in older women of child-bearing age. Strategies to reduce the impact of cyclophosphamide on ovarian reserve as well as fertility preservation technologies are options to consider when treating immune-mediated CKD. A multidisciplinary approach in counseling the woman with CKD who wishes to contemplate or avoid pregnancy is necessary to optimize outcomes. Further research in this important area is required.

Gonadotropin-releasing hormone agonists for the preservation of ovarian function among women with breast cancer who did not use tamoxifen after chemotherapy: a systematic review and meta-analysis.

OBJECTIVE: To determine whether concurrent use of GnRH agonists with chemotherapy preserves ovarian function in women with breast cancer who did not use tamoxifen. DESIGN: Systematic review and meta-analysis. SETTING: University-based hospitals. PATIENT(S): Premenopausal women with breast cancer treated with chemotherapy who did not receive tamoxifen. INTERVENTION(S): Randomization to concurrent GnRH agonists with chemotherapy or chemotherapy alone. MAIN OUTCOME MEASURE(S): Odds ratio (OR) of resumption of menses 1 year or more after chemotherapy. RESULT(S): Searches were conducted in PubMed, Scopus, Cochrane Trials Register, and the National Research Register through March 2014, and all randomized trials that reported resumption of menses 1 year or more after GnRH agonist with chemotherapy or chemotherapy alone among women with breast cancer who did not receive tamoxifen were included. Four studies were analyzed in the meta-analysis and included 252 patients (GnRH agonist with chemotherapy, n=131; chemotherapy alone, n=121). There was no significant difference in the rate of return of menses between the two groups (OR, 1.47; 95% confidence interval [0.60-3.62]). Heterogeneity among the trials was not significant (I2=16.6%). CONCLUSION(S): Concurrent GnRH agonists with chemotherapy may not preserve ovarian function in women with breast cancer. Furthermore, randomized data are limited regarding fertility after concurrent use of GnRH agonists with chemotherapy.

Perceptions and acceptance of immunization during pregnancy.

OBJECTIVE: To estimate patients' perceptions of the need, safety and acceptability of vaccination during pregnancy. STUDY DESIGN: An office-based survey was offered to patients presenting for obstetric and gynecologic care from December 2007 to July 2008 at an academic women's hospital. The anonymous questionnaire assessed demographics, medical and vaccination history, interest in receiving vaccines, and beliefs about vaccination safety. Data were evaluated using descriptive statistics and chi2 analyses. RESULTS: A total of 1,436 completed surveys were available for analysis, including 573 from pregnant women. Pregnant women were less likely than non-pregnant women to report perceived risks from vaccine-preventable illness (22.8% vs. 34.5%, p < 0.001) and to believe that their doctor thinks they should get vaccines (42.6% vs. 49.7%, p < 0.027). Nearly two-thirds (61%) reported concern about possible vaccine effects on their pregnancy. However, the overwhelming majority (89%) of pregnant women surveyed reported willingness to accept vaccination during pregnancy if recommended by their obstetrician. CONCLUSION: Despite concerns about vaccine safety and a low perceived need for immunization, most pregnant respondents endorse acceptance of vaccination when recommended by their obstetrician. These findings suggest that obstetric providers should maximize opportunities for uptake of appropriate immunizations during pregnancy.

Management of the first in vitro fertilization cycle for unexplained infertility: a cost-effectiveness analysis of split in vitro fertilization-intracytoplasmic sperm injection.

OBJECTIVE: To determine the cost-effectiveness of split IVF-intracytoplasmic sperm injection (ICSI) for the treatment of couples with unexplained infertility. DESIGN: Adaptive decision model. SETTING: Academic infertility clinic. PATIENT(S): A total of 154 couples undergoing a split IVF-ICSI cycle and a computer-simulated cohort of women <35 years old with unexplained infertility undergoing IVF. INTERVENTION(S): Modeling insemination method in the first IVF cycle as all IVF, split IVF-ICSI, or all ICSI, and adapting treatment based on fertilization outcomes. MAIN OUTCOME MEASURE(S): Live birth rate, incremental cost-effectiveness ratio (ICER). RESULT(S): In a single cycle, all IVF is preferred as the ICER of split IVF-ICSI or all ICSI ($58,766) does not justify the increased live birth rate (3%). If two cycles are needed, split IVF/ICSI is preferred as the increased cumulative live birth rate (3.3%) is gained at an ICER of $29,666. CONCLUSION(S): In a single cycle, all IVF was preferred as the increased live birth rate with split IVF-ICSI and all ICSI was not justified by the increased cost per live birth. If two IVF cycles are needed, however, split IVF/ICSI becomes the preferred approach, as a result of the higher cumulative live birth rate compared with all IVF and the lesser cost per live birth compared with all ICSI.

Estrogen-suppressed in vitro maturation: a novel approach to in vitro maturation.

OBJECTIVE: To evaluate the laboratory and clinical outcomes of estrogen-suppressed in vitro maturation (ES-IVM), a novel IVM protocol that eliminates the need for FSH stimulation and cycle monitoring. DESIGN: Case series. SETTING: Academic infertility center. PATIENT(S): Eighteen infertile couples undergoing ES-IVM (n = 20). Eligible candidates included women ≤38 years old with either polycystic ovarian syndrome, antral follicle count ≥15, and/or history of ovarian hyperstimulation syndrome. INTERVENTION(S): ES-IVM. MAIN OUTCOMES MEASURE(S): Oocyte yield, maturation, fertilization, embryo quality, implantation, clinical pregnancy, and live-birth rate were analyzed. RESULT(S): The average number of oocytes retrieved was 16.7 ± 5.9, with a 52.1% maturation rate and a 58% fertilization rate by intracytoplasmic sperm injection. The average number of embryos transferred was 2.85 ± 0.6. The implantation rate was 17.5%, the clinical pregnancy rate was 40%, and the live-birth rate was 40%. CONCLUSION(S): The efficiency of ES-IVM appears to be similar to natural cycle and low-stimulation IVM protocols with respect to laboratory and clinical outcomes, while eliminating the need for FSH stimulation and cycle monitoring.

Vaccine eligibility and acceptance among ambulatory obstetric and gynecologic patients.

OBJECTIVE: To assess vaccine eligibility and factors associated with vaccine acceptance among ambulatory obstetric and gynecologic patients. METHODS: An anonymous office-based survey was administered to women seeking ambulatory obstetric and gynecologic care at a large women's hospital from December 2007 to July 2008. Information collected included: demographics, medical and vaccination history, interest in receiving vaccines and attitudes towards vaccine providers. Vaccine eligibility was based on age and/or self-reported risk factors in accord with the 2007-2008 Center for Disease Control and Prevention (CDC) adult immunization schedule. Vaccine eligibility was examined using descriptive statistics, and demographic characteristics were compared using chi-squared analysis. A multivariable logistic regression model was developed to assess factors associated with participants' willingness to accept vaccines from their obstetrician-gynecologist. RESULTS: A total of 1441 women completed the survey. The majority of participants (87%) would accept vaccines if recommended by their obstetrician-gynecologist. The primary factors associated with vaccine acceptance were having less than a high school education, being privately insured, currently being pregnant, reporting a history of vaccinations and previously receiving vaccinations from an obstetrician-gynecologist. A significant portion of participants were eligible for the hepatitis B, influenza and HPV vaccines (≥ 50% for each). The type of vaccine did not influence willingness to accept vaccines from an obstetrician-gynecologist. CONCLUSION: A majority of women appear eligible for, and will accept, vaccinations regardless of specific vaccine, if recommended by their obstetrician-gynecologist. These findings justify ongoing efforts to expand immunization services offered by obstetrician-gynecologists.