Parenthood and the physical and mental health of sexual and gender minority parents: A cross-sectional, observational analysis from The PRIDE Study.

PURPOSE: To compare the physical and mental health of sexual and gender minority (SGM) parents to SGM non-parents. METHODS: A cross-sectional analysis using 2018-2020 data from The PRIDE Study, a national longitudinal cohort of SGM adults. We used Poisson regression adjusted for age, gender, relationship status, race/ethnicity, household income, and education to assess the association between parental status and each outcome. RESULTS: Among 9625 SGM participants, 1460 (15 %) were parents. Older participants were more likely to be parents: 2% of participants aged 18-30, 18% aged 30-39, and 38% aged 40+ were parents. In adjusted analyses, parenthood was associated with greater depression, anxiety, and post-traumatic stress symptoms as well as ever cigarette smoking. Among individuals assigned female sex at birth, parents were twice as likely to have been diagnosed with pelvic inflammatory disease compared to non-parents. There was no association between parenthood status and alcohol use, substance use, diabetes, HIV, hypertension, or autism. CONCLUSIONS: In this national cohort of SGM adults, parenthood was associated with differences in physical and mental health measures. Understanding how parenthood influences the health and well-being of the estimated 3 million SGM parents in the US will help our health systems support diverse families.

Differences in medically assisted reproduction use by sexual identity and partnership: a prospective cohort of cisgender women.

STUDY QUESTION: Does medically assisted reproduction (MAR) use among cisgender women differ among those with same-sex partners or lesbian/bisexual identities compared to peers with different-sex partners or heterosexual identities? SUMMARY ANSWER: Women with same-sex partners or lesbian/bisexual identities are more likely to utilize any MAR but are no more likely to use ART (i.e. IVF, reciprocal IVF, embryo transfer, unspecified ART, ICSI, and gamete or zygote intrafallopian transfer) compared to non-ART MAR (i.e. IUI, ovulation induction, and intravaginal or intracervical insemination) than their different-sex partnered and completely heterosexual peers. WHAT IS KNOWN ALREADY: Sexual minority women (SMW) form families in myriad ways, including through fostering, adoption, genetic, and/or biological routes. Emerging evidence suggests this population increasingly wants to form genetic and/or biological families, yet little is known about their family formation processes and conception needs. STUDY DESIGN, SIZE, DURATION: The Growing Up Today Study is a US-based prospective cohort (n = 27 805). Participants were 9-17 years of age at enrollment (1996 and 2004). Biennial follow-up is ongoing, with data collected through 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cisgender women who met the following criteria were included in this sample: endorsed ever being pregnant; attempted a pregnancy in 2019 or 2021; and endorsed either a male- or female-sex partner OR responded to questions regarding their sexual identity during their conception window. The main outcome was any MAR use including ART (i.e. procedures involving micromanipulation of gametes) and non-ART MAR (i.e. nonmanipulation of gametes). Secondary outcomes included specific MAR procedures, time to conception, and trends across time. We assessed differences in any MAR use using weighted modified Poisson generalized estimating equations. MAIN RESULTS AND THE ROLE OF CHANCE: Among 3519 participants, there were 6935 pregnancies/pregnancy attempts and 19.4% involved MAR. A total of 47 pregnancies or pregnancy attempts were among the same-sex partnered participants, while 91 were among bisexual participants and 37 among lesbian participants. Participants with same-sex, compared to different-sex partners were almost five times as likely to use MAR (risk ratio [95% CI]: 4.78 [4.06, 5.61]). Compared to completely heterosexual participants, there was greater MAR use among lesbian (4.00 [3.10, 5.16]) and bisexual (2.22 [1.60, 3.07]) participants compared to no MAR use; mostly heterosexual participants were also more likely to use ART (1.42 [1.11, 1.82]) compared to non-ART MAR. Among first pregnancies conceived using MAR, conception pathways differed by partnership and sexual identity groups; differences were largest for IUI, intravaginal insemination, and timed intercourse with ovulation induction. From 2002 to 2021, MAR use increased proportionally to total pregnancies/pregnancy attempts; ART use was increasingly common in later years among same-sex partnered and lesbian participants. LIMITATIONS, REASONS FOR CAUTION: Our results are limited by the small number of SMW, the homogenous sample of mostly White, educated participants, the potential misclassification of MAR use when creating conception pathways unique to SMW, and the questionnaire's skip logic, which excluded certain participants from receiving MAR questions. WIDER IMPLICATIONS OF THE FINDINGS: Previous studies on SMW family formation have primarily focused on clinical outcomes from ART procedures and perinatal outcomes by conception method, and have been almost exclusively limited to European, clinical samples that relied on partnership data only. Despite the small sample of SMW within a nonrepresentative study, this is the first study to our knowledge to use a nonclinical sample of cisgender women from across the USA to elucidate family formation pathways by partnership as well as sexual identity, including pathways that may be unique to SMW. This was made possible by our innovative approach to MAR categorization within a large, prospective dataset that collected detailed sexual orientation data. Specifically, lesbian, bisexual, and same-sex partnered participants used both ART and non-ART MAR at similar frequencies compared to heterosexual and different-sex partnered participants. This may signal differential access to conception pathways owing to structural barriers, emerging conception trends as family formation among SMW has increased, and a need for conception support beyond specialized providers and fertility clinics. STUDY FUNDING/COMPETING INTEREST(S): The research reported in this publication was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health (NIH), under award number R01MD015256. Additionally, KRSS is supported by NCI grant T32CA009001, AKH by the NCI T32CA057711, PC by the NHLBI T32HL098048, BM by the Stanford Maternal Child Health Research Institute Clinical Trainee Support Grant and the Diversity Fellowship from the American Society for Reproductive Medicine Research Institute, BGE by NICHD R01HD091405, and SM by the Thomas O. Pyle Fellowship through the Harvard Pilgrim Health Care Foundation and Harvard University, NHLBI T32HL098048, NIMH R01MH112384, and the William T. Grant Foundation grant number 187958. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The first author recently had a leadership role in the not-for-profit program, The Lesbian Health Fund, a research fund focused on improving the health and wellbeing of LGBTQ+ women and girls. The fund did not have any role in this study and the author's relationship with the fund did not bias the findings of this manuscript. TRIAL REGISTRATION NUMBER: N/A.

Factors Associated with Provider Counseling Against Breastfeeding in the Setting of Marijuana Use: A Population-Based Survey.

INTRODUCTION: The purpose of this study was to explore patient demographic factors associated with counseling against breastfeeding and concurrent marijuana use. METHODS: A cross-sectional study derived using data from the Centers for Disease Control and Prevention administered Pregnancy Risk Assessment Monitoring System (PRAMS) in collaboration with state and local health departments. This study sample included survey participants whose responses indicate they received counseling discouraging breastfeeding with concurrent marijuana use. Bivariate and multivariate regression analyses assessed the relationship between factors associated with counseling against breastfeeding and concurrent marijuana use. RESULTS: Of the 10,911 participants in this sample, 9,695 participants who answered the question about receiving counseling discouraging breastfeeding while using marijuana were included in the analysis (89% response rate for the total sample). Twenty nine percent of participants were advised by a provider not to breastfeed while using marijuana. Participants who received this counseling were more likely to be people of color, age less than or equal to 29, with a high school education or less, unmarried, report governmental or no insurance prepregnancy, and report marijuana use postpartum. In the multivariate analysis, age less than or equal to 20 (P = .001), being unmarried (P = .023), and marijuana use postpartum (P = .034) remained associated with counseling against breastfeeding. DISCUSSION: Our results suggest that individuals are being counseled differently. Unmarried and young people (age <20 years) were more likely to report receiving counseling against breastfeeding with concurrent marijuana use. Given the growing national acceptability of marijuana use, the known benefits of breastfeeding, and the unclear risks of marijuana in human milk, there is a need to standardize counseling to avoid a missed opportunity to educate breastfeeding populations who use marijuana and to reduce the risk of counseling based on providers' personal attitudes and biases not aligned with evidence-based guidelines.

Shared IVF among female couples: clinical outcomes of the Reception of Oocytes from the Partner (ROPA) method.

RESEARCH QUESTION: What is the population undergoing the ROPA (Reception of Oocytes from Partner) method and what are the outcomes of the technique? DESIGN: Case series of all ROPA treatments carried out between 2011 and 2020 in 18 fertility clinics in Spain. Demographic characteristics, cycle features, laboratory and clinical outcomes, and the intentions regarding the disposition of surplus embryos were analysed. RESULTS: Donor patients were on average 3.5 years younger than recipients (P = 0.001). No significant differences were found in body mass index or anti-Müllerian hormone. In 13% of cases, fertility issues were found: poor ovarian reserve (6.8%); endometriosis (2.9%); and polycystic ovary syndrome (2.2%). Including cases of advanced age (38 years old or older), more than one-half of couples (53.6%) had some condition that could affect fertility. Mean number of mature oocytes per cycle was 10 (+/- 5.7), and fertilization rate was 74.5% (+/- 18.8). Mean number of viable embryos was 3.2 (+/- 1.5). Surplus embryos were cryopreserved in 50.4% of cycles. Outcomes after embryo transfers from ROPA, and subsequent frozen cycles were as follows: positive pregnancy test (61.0%), clinical pregnancy (54.1%) and miscarriage rate (16.1%). Other outcomes were live birth rate per embryo transfer (44.7%); multiple pregnancy rate (5.4%); per cumulative ROPA cycle (48.6%); and per couple (61.6%). CONCLUSION: The outcomes of the ROPA method are reassuring. About one-half of the ROPA cycles resulted in a live birth and one-quarter of the cycles had surplus embryos after achieving a live birth. Main neonatal outcomes were also reassuring.

Reproductive endocrinologist and infertility specialists' knowledge, skills, behaviors, and attitudes regarding the care for transgender and gender-diverse individuals.

Objective: To investigate associations between reproductive endocrinology and infertility (REI) providers' prior training and current knowledge, skills, attitudes, and behaviors regarding fertility preservation and family building for transgender and gender-diverse (T/GD) patients. Design: The survey was distributed to members of the Society for Reproductive Endocrinology and Infertility, the REI-physician-focused professional body within the American Society for Reproductive Medicine, with additional participants recruited through snowball sampling. Results: Participants (n = 206) reported on training in T/GD care; 51% endorsed prior training. Most participants (93%) believed T/GD individuals were as fit for parenthood as cisgender individuals. Prior training was associated with an increased likelihood of offering T/GD health resources and more frequent consultations with specialist colleagues.Common barriers to providing care indicated by respondents included cost, delays in gender-affirming care, and lack of knowledge of the potential impact of hormonal interventions. Common facilitators included education and training, prior experience, and affordability of services. Conclusions: Most REI providers believed T/GD individuals are fit for parenthood and agreed that prior training facilitates care for T/GD patients. The lack of provider knowledge emerged as a barrier to care. Although training helped facilitate some components of care, systemic barriers such as the cost and variability of patient population characteristics/experiences are important considerations when serving T/GD individuals.

Oocyte and embryo cryopreservation in assisted reproductive technology: past achievements and current challenges.

Cryopreservation has revolutionized the treatment of infertility and fertility preservation. This review summarizes the milestones that paved the way to the current routinary clinical implementation of this game-changing practice in assisted reproductive technology. Still, evidence to support "the best practice" in cryopreservation is controversial and several protocol adaptations exist that were described and compared here, such as cumulus-intact vs. cumulus-free oocyte cryopreservation, artificial collapse, assisted hatching, closed vs. open carriers, and others. A last matter of concern is whether cryostorage duration may impact oocyte/embryo competence, but the current body of evidence in this regard is reassuring. From social and clinical perspectives, oocyte and embryo cryopreservation has evolved from an afterthought when assisted reproduction was intended for immediate pregnancy with supernumerary embryos of secondary interest to its current purpose, which primarily is to preserve fertility long-term and more comprehensively allow for family planning. However, the initial consenting process, which still is geared to short-term fertility care, may no longer be relevant when the individuals that initially preserved the tissues have completed their reproductive journey. A more encompassing counseling model is required to address changing patient values over time.

Pathways to fatherhood: clinical experiences with assisted reproductive technology in single and coupled intended fathers.

Objective: To explore the cycle characteristics and outcomes of single and coupled intended fathers (SCIFs) using assisted reproductive technology. Design: Cross-sectional study. Setting: Multicenter, fertility practices from 2016 to 2020. Patients: In this study, cycles among SCIFs with access to fertility coverage from 2016 to 2020 were included. Interventions: None. Main Outcome Measures: Our primary outcome was live birth rate. The secondary outcomes included the number of embryos transferred, miscarriage rate, and incidence of multifetal birth. Results: Five single and 39 coupled intended fathers completed an in vitro fertilization cycle with a majority using egg donation and an agency-based gestational carrier (69.7%, 83/119). In most couples, both partners wanted to serve as the sperm source (64.4%, 29/45). The vast majority (97.7%, 43/44) also used preimplantation genetic testing for aneuploidy. Among the embryo transfer (ET) cycles (n = 27), most consisted of a single euploid ET (74.07%, 20/27), whereas the remaining consisted of a double euploid ET (25.92%, 7/27). The SCIFs had high rates of success, with a live birth rate of 85.19% (23/27). A mean of 1.26 ± 0.44 embryos were transferred, with a majority resulting in singleton birth (70.37%, 19/27). Conclusions: Our study of SCIFs using assisted reproductive technology in the United States demonstrates that this population shares similar preferences for sperm source and the use of preimplantation genetic testing. Clinical outcomes suggest that this population is successful at achieving a live birth when using egg donation and a gestational carrier.

Sexual and/or gender minority disparities in obstetrical and birth outcomes.

BACKGROUND: Many sexual and/or gender minority individuals build families through pregnancy and childbirth, but it is unknown whether they experience different clinical outcomes than those who are not sexual and/or gender minority individuals. OBJECTIVE: To evaluate obstetrical and birth outcomes comparing couples who are likely sexual and/or gender minority patients compared with those who are not likely to be sexual and/or gender minority patients. STUDY DESIGN: We performed a population-based cohort study of live birth hospitalizations during 2016 to 2019 linked to birth certificates in California. California changed its birth certificate in 2016 to include gender-neutral fields such as "parent giving birth" and "parent not giving birth," with options for each role to specify "mother," "father," or "parent." We classified birthing patients in mother-mother partnerships and those who identified as a father in any partnership as likely sexual and/or gender minority and classified birthing patients in mother-father partnerships as likely not sexual and/or gender minority. We used multivariable modified Poisson regression models to estimate the risk ratios for associations between likely sexual and/or gender minority parental structures and outcomes. The models were adjusted for sociodemographic factors, comorbidities, and multifetal gestation selected by causal diagrams. We replicated the analyses after excluding multifetal gestations. RESULTS: In the final birthing patient sample, 1,483,119 were mothers with father partners, 2572 were mothers with mother partners, and 498 were fathers with any partner. Compared with birthing patients in mother-father partnerships, birthing patients in mother-mother partnerships experienced significantly higher rates of multifetal gestation (adjusted risk ratio, 3.9; 95% confidence interval, 3.4-4.4), labor induction (adjusted risk ratio, 1.2; 95% confidence interval, 1.1-1.3), postpartum hemorrhage (adjusted risk ratio, 1.4; 95% confidence interval, 1.3-1.6), severe morbidity (adjusted risk ratio, 1.4; 95% confidence interval, 1.2-1.8), and nontransfusion severe morbidity (adjusted risk ratio, 1.4; 95% confidence interval, 1.1-1.9). Severe morbidity was identified following the Centers for Disease Control and Prevention "severe maternal morbidity" index. Gestational diabetes mellitus, hypertensive disorders of pregnancy, cesarean delivery, preterm birth (<37 weeks' gestation), low birthweight (<2500 g), and low Apgar score (<7 at 5 minutes) did not significantly differ in the multivariable analyses. No outcomes significantly differed between father birthing patients in any partnership and birthing patients in mother-father partnerships in either crude or multivariable analyses, though the risk of multifetal gestation was nonsignificantly higher (adjusted risk ratio, 1.5; 95% confidence interval, 0.9-2.7). The adjusted risk ratios for the outcomes were similar after restriction to singleton gestations. CONCLUSION: Birthing mothers with mother partners experienced disparities in several obstetrical and birth outcomes independent of sociodemographic factors, comorbidities, and multifetal gestation. Birthing fathers in any partnership were not at a significantly elevated risk of any adverse obstetrical or birth outcome considered in this study.

An assessment of oncofertility content on reproductive endocrinology and infertility clinic websites.

PURPOSE: To assess oncofertility content on fertility clinic websites as indicated by eight relevant keywords. Additionally, we sought to describe the relationship between oncofertility content and five predetermined clinic characteristics. METHODS: We examined 381 fertility clinic websites that are members of the Society for Associated Reproductive Technology (SART). Extracted data included clinic location, practice type (private vs academic), size (cycles/year), type of NCI designated center (cancer center vs comprehensive cancer center), and distance from the nearest NCI center. Additionally, we documented whether the clinic was located in a state mandating reproductive and infertility services and/or included fertility preservation for "iatrogenic infertility" as reported by the American Society for Reproductive Medicine (ASRM). Data were summarized using descriptive statistics and compared using chi-squared or t-test as appropriate. RESULTS: Of the 381 fertility clinic websites analyzed, 322 (85%) contained at least one oncofertility-related keyword. Most frequently used terms included cancer (79%) and fertility preservation (78%), while less frequently used terms included suppression (9.4%) and shielding (5.0%). Practices that initiated ≥ 501 cycles per year were more likely to mention one of the oncofertility keywords (OR 1.2; 95% CI 1.1-1.3). The associations of oncofertility website content with practice type, state-mandated fertility insurance coverage, and distance from an NCI-designated cancer center were not statistically significant. Large clinic size was the only predictive factor for inclusion of oncofertility website content. Further studies are required to evaluate whether inclusion of oncofertility content on clinic websites impacts the use of these services by patients with cancer. CONCLUSION: This is the first study correlating availability of oncofertility content on SART fertility clinic websites with consideration of geographic proximity to NCI designated cancer centers. Large clinic size was the only predictive factor for inclusion of oncofertility website content.

Is living in a region with high groundwater arsenic contamination associated with adverse reproductive health outcomes? An analysis using nationally representative data from India.

BACKGROUND: Exposure to groundwater arsenic via drinking water is common in certain geographies, such as parts of India, and causes a range of negative health effects, potentially including adverse reproductive health outcomes. METHODS: We conducted an ecological analysis of self-reported rates of stillbirth, recurrent pregnancy loss, and infertility in relation to groundwater arsenic levels in India. We used a gridded, modeled dataset of the probability of groundwater arsenic exceeding 10 µg/L (World Health Organization drinking water limit) to calculate mean probabilities at the district level (n = 599 districts). A spatial integration approach was used to merge these estimates with the third India District-Level Health Survey (DLHS-3) conducted in 2007-08 (n = 643,944 women of reproductive age). Maps of district level arsenic levels and rates of each of the three outcomes were created to visualize the patterns across India. To adjust for significant spatial autocorrelation, spatial error models were fit. FINDINGS: District-level analysis showed that the average level of stillbirth was 4.3%, recurrent pregnancy loss was 3.3%, and infertility was 8.1%. The average district-level probability of groundwater arsenic levels exceeding 10 µg/L was 42%. After adjustment for sociodemographic factors, and accounting for spatial dependence, at the district level, for each percentage point increase in predicted arsenic levels exceeding 10 µg/L increased, the rates of stillbirths was 4.5% higher (95% confidence interval (CI) 2.4-6.6, p < 0.0001), the rates of RPL are 4.2% higher (95% CI 2.5-5.9, p < 0.0001), and the rates of infertility are 4.4% higher (95% CI 1.2-7.7, p=<0.0001).). CONCLUSIONS: While arsenic exposure has been implicated with a range of adverse health outcomes, this is one of the first population-level studies to document an association between arsenic and three adverse reproductive pregnancy outcomes. The high levels of spatial correlation suggest that further and targeted efforts to mitigate arsenic in groundwater are needed.

Bellagio II Report: Terrestrial Applications of Space Medicine Research.

AbstractINTRODUCTION: For over 50 yr, investigators have studied the physiological adaptations of the human system during short- and long-duration spaceflight exposures. Much of the knowledge gained in developing health countermeasures for astronauts onboard the International Space Station demonstrate terrestrial applications. To date, a systematic process for translating these space applications to terrestrial human health has yet to be defined.METHODS: In the summer of 2017, a team of 38 international scientists launched the Bellagio ll Summit Initiative. The goals of the Summit were: 1) To identify space medicine findings and countermeasures with highest probability for future terrestrial applications; and 2) To develop a roadmap for translation of these countermeasures to future terrestrial application. The team reviewed public domain literature, NASA databases, and evidence books within the framework of the five-stage National Institutes of Health (NIH) translation science model, and the NASA two-stage translation model. Teams then analyzed and discussed interdisciplinary findings to determine the most significant evidence-based countermeasures sufficiently developed for terrestrial application.RESULTS: Teams identified published human spaceflight research and applied translational science models to define mature products for terrestrial clinical practice.CONCLUSIONS: The Bellagio ll Summit identified a snapshot of space medicine research and mature science with the highest probability of translation and developed a Roadmap of terrestrial application from space medicine-derived countermeasures. These evidence-based findings can provide guidance regarding the terrestrial applications of best practices, countermeasures, and clinical protocols currently used in spaceflight.Sides MB, Johnston SL III, Sirek A, Lee PH, Blue RS, Antonsen EL, Basner M, Douglas GL, Epstein A, Flynn-Evans EE, Gallagher MB, Hayes J, Lee SMC, Lockley SW, Monseur B, Nelson NG, Sargsyan A, Smith SM, Stenger MB, Stepanek J, Zwart SR; Bellagio II Team. Bellagio II report: terrestrial applications of space medicine research. Aerosp Med Hum Perform. 2021; 92(8):650669.

The Influence of PrEP-Related Stigma and Social Support on PrEP-Use Disclosure among Women Who Inject Drugs and Social Network Members.

Pre-exposure prophylaxis (PrEP) is a promising but underutilized HIV prevention strategy for Women who Inject Drugs (WWID). Stigma and disclosure concerns have been key barriers to PrEP use among women in PrEP efficacy trials. Social support has been found to buffer against some PrEP stigma, though these factors have been largely unexplored among WWID. Investigating how WWID disclose PrEP use is important given evidence that disclosure is associated with higher adherence. We aimed to identify the impact of stigma and support on PrEP disclosure within social networks of WWID participating in a PrEP demonstration project in Philadelphia, PA, USA. PrEP-using WWID ≥ 18 years completed social network surveys. Generalized estimating equations were used to account for the correlation of network structure. Thirty-nine WWID (i.e. egos) named an average of 9.5 ± 3.3 network members (i.e. alters), for a total sample of 371 unique relationships. Egos disclosed their PrEP use to an average of 4.0 alters (SD = 2.8). Related to PrEP stigma, participants had 0.4 times decreased odds of PrEP disclosure with alters who would disapprove of them taking PrEP (95% CI: 0.1-0.9). Related to support, participants had 2.5 times higher odds of disclosure among peers who could provide PrEP advice (95% CI: 1.0-6.0). Interventions that increase social support and decrease stigma are pivotal for increasing PrEP use disclosure among WWID.

Operative Vaginal Birth of a Critically Endangered Gorilla With Forceps Assistance.

BACKGROUND: An obstetrician on standby assessed an 18-year-old primiparous captive gorilla with a term singleton fetus with a protracted labor course. CASE: After it was determined that an arrest of descent had occurred, a viable, 2,280 g male neonate was delivered through an operative vaginal birth with forceps assistance without major complications. CONCLUSION: Given the numerous anatomic and biochemical similarities of humans and other great apes, it is possible that the high maternal mortality and stillbirth rates of gorillas could be reduced by using the same principles of obstetric management in a multidisciplinary fashion.

Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yield.

PURPOSE: To investigate how biologic age (phenotypic age at which your body functions) greater than chronologic age, (age acceleration (AgeAccel)), correlates with oocyte yield. METHODS: Thirty-nine women undergoing ovarian stimulation, inclusive of all infertility diagnoses, were included in this pilot study. Methylome analysis of peripheral blood was utilized to determine biologic age. AgeAccel was defined as biologic age > 2 years older than chronologic age. A negative binomial model was used to obtain the crude association of AgeAccel with number of oocytes. A parsimonious adjusted model for the number of oocytes was obtained using backwards selection (p < 0.05). RESULTS: Measures of age were negatively correlated with number of oocytes (chronological age Pearson ρ = - 0.45, biologic age Pearson ρ = - 0.46) and AMH was positively correlated with number of oocytes (Pearson ρ = 0.91). Patients with AgeAccel were noted to have lower AMH values (1.29 ng/mL vs. 2.29, respectively (p = 0.049)) and lower oocyte yield (5.50 oocytes vs. 14.50 oocytes, respectively (p = 0.0030)). A crude association of a 7-oocyte reduction in the age-accelerated group was found (- 6.9 oocytes (CI - 11.6, - 2.4)). In a model with AMH and antral follicle count, AgeAccel was associated with a statistically significant 3.3 reduction in the number of oocytes (- 3.1; 95% CI - 6.5, - 0.1; p = 0.036). CONCLUSIONS: In this small pilot study, AgeAccel is associated with a lower AMH and lower oocyte yield providing preliminary evidence that biologic age, specifically AgeAccel, may serve as an epigenetic biomarker to improve the ability of predictive models to assess ovarian reserve.

Diagnosis and clinical delineation of mosaic tetrasomy 5p.

OBJECTIVE: Our objective was to review the phenotypic and genetic characteristics of tetrasomy 5p from the fetal period until adulthood including prenatal diagnostic evaluations. BACKGROUND: Tetrasomy 5p is a rare chromosomal abnormality. Of the 14 reports, most document mosaic tetrasomy 5p resulting from a supernumerary marker chromosome or isochromosome. There is a wide range of phenotypic manifestations with severity related to more proximal breakpoints and the degree of mosaicism. DESIGN: We conducted a systematic review using Scopus, PubMed Central® and Ovid MEDLINE® from inception through July 1, 2018 for all articles describing tetrasomy 5p. All articles describing the syndrome of tetrasomy 5p were included. RESULTS: Of the 15 included cases, 13 exhibited mosaic tetrasomy and two had complete tetrasomy identified by amniocentesis. The most common features include seizures (8/11 live births, 73%), hypotonia (7/11 live births, 64%), developmental delay (7/9 cases that reached childhood, 78%), abnormal external ears (6/11 live births, 55%), short stature (6/11 live births, 55%), ventriculomegaly (5/11 live births, 45.5%) and congenital heart defect (6/15 cases, 40%). The clinical phenotype ranged in severity from mild with no defining characteristics to severe with seizures, developmental delay, and multiple congenital anomalies, resulting in early death. Of these 15 cases, only 6 were diagnosed prenatally by prenatal genetic testing (40%) with prenatal ultrasound identifying abnormalities in 4/6 (67%). Confined placental mosaicism (CPM) was diagnosed in six additional cases due to discordance between CVS and amniocentesis results. Four of the five live births returned for evaluation and each showed normal development. CONCLUSIONS: Fourteen out of 15 (93%) cases of tetrasomy 5p were associated with an abnormal phenotype. Once a diagnosis is made prenatally, a detailed anatomy ultrasound and fetal echocardiogram must be performed to further characterize any structural abnormalities of the fetus and potentially estimate the clinical severity. Caution should be exercised when prenatal diagnosis of mosaic tetrasomy 5p is found by chorionic villus sampling. CVS alone is insufficient to diagnose tetrasomy 5p and needs to be confirmed with amniocentesis. Our review seeks to inform clinicians on the current literature regarding tetrasomy 5p so that they may better counsel patients when this syndrome is diagnosed.

Double intrauterine insemination (IUI) of no benefit over single IUI among lesbian and single women seeking to conceive.

PURPOSE: To explore clinical benefit of performing two intrauterine inseminations (IUI) 24 h apart-a double IUI vs. a single IUI among lesbian and single women. METHODS: Retrospective cohort study using electronic medical record review during a 17-year period (11/1999-3/2017). A total of 11,396 patients at a single academic-affiliated private practice were included in this study. All cycles with a single or double IUI were included. A sub-analysis of first cycles only (n = 10,413) was also performed. Canceled IVF cycles converted to IUI were excluded. T tests and Wilcoxon rank-sum tests were used for continuous data, and chi-square for categorical data. Multivariable logistic regression controlled for patient age, day 3 follicle-stimulating hormone (D3 FSH), body mass index (BMI), peak estradiol (E2), and post-wash total motile sperm counts to model the association between IUI number and ongoing pregnancy rate (OPR) according to sperm source (autologous vs. donor). Generalized estimating equations and mixed effect models accounted for multiple cycles from the same woman. Adjusted odds ratio (AOR) with 95% CI was determined. Sub-analyses of sexual orientation and partner status were performed to compare heterosexual couples with proven infertility to women with lesbian and single women. RESULTS: During the study period, 22,452 cycles met inclusion criteria (single IUI 1283 vs. double IUI 21,169). Mean patient age and BMI were similar between groups. For couples using autologous sperm, OPR was significantly higher with double IUI (12.0% vs. 14.1%; p = 0.0380). A similar increase was observed for donor sperm OPR among heterosexual couples (14.4% vs. 16.2%), though this did not reach statistical significance (p = 0.395). A sub-analysis restricted to donor sperm demonstrates a clinical benefit of second IUI in heterosexual couples, 8.5% vs. 17.6% OPR (AOR 2.94; CI 1.00-10.99; p = 0.0496). When lesbian and single patients were evaluated, there was no difference (17.2% vs. 15.2%; AOR 0.99; CI 0.59-1.70; p = 0.0958). CONCLUSIONS: Double IUI is associated with a significantly higher OPR for heterosexual couples using an autologous or donor sperm source. The benefit of a second IUI is less clear in patients with undocumented fertility status using donor sperm, such as single and lesbian women.

Hypertensive disorders of pregnancy and infertility treatment: a population-based survey among United States women.

PURPOSE: To explore associations between infertility treatment and hypertensive disorders of pregnancy. METHODS: We collated multi-year as well as multi-state data from a national representative survey examining the association between self-reported infertility treatment (i.e., medication, intrauterine insemination, or assisted reproductive technology) and hypertensive disorders of pregnancy (i.e., high blood pressure, pregnancy-induced hypertension (PIH), preeclampsia, and toxemia). Data were analyzed using logistic regression. A total of 21,884 women in the United States (U.S.), from the Centers for Disease Control and Prevention's (CDC) Pregnancy Risk Assessment Monitoring System (PRAMS) survey (2009-2015), participated in the study. RESULTS: In our analysis, 12.91% women reported a history of infertility treatment and 15.19% reported a history of hypertensive disorder of pregnancy. Compared with women who had never had infertility treatment, women who reported infertility treatment had 1.18 (adjusted OR, 95% confidence interval (CI) 1.05, 1.33) higher odds of reporting hypertensive disorder of pregnancy. Neither types of infertility treatment nor proximity of treatment to pregnancy were independently associated with hypertensive disorder of pregnancy. CONCLUSIONS: Our results suggest that among U.S. women, the treatment of infertility may be associated with hypertension disorder of pregnancy regardless of type of treatment.

Review of familial hemiplegic migraine, successful outcome in a pregnant patient.

As the field of neurogenetics is expanding rapidly and variant classification criteria evolve, genetic variants in databases are re-evaluated overtime allowing updated classifications of pathogenicity predication. When caring for patients with genetic disorders, it is important to obtain the original genetic report and also consider an updated reanalysis.

Use of various gonadotropin and biosimilar formulations for in vitro fertilization cycles: results of a worldwide Web-based survey.

PURPOSE: The purpose of this study was to identify trends in gonadotropin therapy in patients undergoing in vitro fertilization (IVF) treatment worldwide. METHODS: Retrospective evaluation utilizing the results of a Web-based survey, IVF-Worldwide ( www.IVF-worldwide.com ) was performed. RESULTS: Three hundred fourteen centers performing a total of 218,300 annual IVF cycles were evaluated. Respondents representing 62.2% of cycles (n = 135,800) did not believe there was a difference between urinary and recombinant gonadotropins in terms of efficacy and live birth rate. Of the respondents, 67.3% (n = 146,800) reported no difference between recombinant and urinary formulations in terms of short-term safety and risk of ovarian hyperstimulation syndrome. In terms of long-term safety using human urinary gonadotropins, 50.6% (n = 110,400) of respondents believe there are potential long-term risks including prion disease. For 95.3% of units (n = 208,000), the clinician was the decision maker determining which specific gonadotropins are used for IVF. Of the units, 62.6% (n = 136,700) identified efficacy as the most important factor in deciding which gonadotropin to prescribe. While most (67.3%, n = 146,800) were aware of new biosimilar recombinant FSH products entering the market, 92% (n = 201,000) reported they would like more information. A fraction of respondents (25.6%, n = 55,900) reported having experience with these new products, and of these, 80.3% (n = 46,200) reported that they were similar in efficacy as previously used gonadotropins in a similar patient group. CONCLUSIONS: Respondents representing the majority of centers do not believe a difference exists between urinary and recombinant gonadotropins with respect to efficacy and live birth rates. While many are aware of new biosimilar recombinant FSH products entering the market, over 90% desire more information on these products.