Association of Early Beta Human Chorionic Gonadotropin With Ischemic Placental Disease in Singleton Pregnancies After In Vitro Fertilization.

OBJECTIVES: To evaluate whether an initial or two-day percent increase in serum beta-human chorionic gonadotropin (ßhCG) is associated with ischemic placental disease (IPD) in singleton pregnancies after autologous or donor IVF. STUDY DESIGN: This was a secondary analysis of a retrospective cohort study of deliveries linked to IVF cycles at a single academic tertiary hospital and infertility treatment center. We included all patients (≥18 years old) who had a singleton live birth or intrauterine fetal demise (IUFD) resulting from either autologous fresh (n=1,347), autologous frozen (n=454), or donor (n=253) IVF cycles. Main outcome reassures: The primary outcome was a composite outcome of IPD or IUFD due to placental insufficiency. IPDs included preeclampsia, placental abruption, and small for gestational age (SGA). RESULTS: Neither initial ßhCG nor two-day percent increases in ßhCG were associated with an increased risk of IPD for any type of IVF cycle. Initial and two-day percent increases in ßhCG were significantly higher when comparing frozen with fresh IVF and donor with autologous IVF (all P≤0.01). CONCLUSIONS: Among singleton autologous and donor IVF cycles, the initial and two-day percent increase in serum ßhCG were not associated with IPD or its components. However, significant ßhCG differences existed by cycle type and oocyte source.

Assisted reproductive technology outcomes in female-to-male transgender patients compared with cisgender patients: a new frontier in reproductive medicine.

OBJECTIVE: To investigate assisted reproductive technology (ART) outcomes in a female-to-male transgender cohort and compare the results with those of a matched cisgender cohort. DESIGN: Matched retrospective cohort study. SETTING: In vitro fertilization clinic. PATIENT(S): Female-to-male transgender patients (n = 26) who sought care from 2010 to 2018. A cisgender cohort (n = 130) was matched during the same time period by age, body mass index, and antimüllerian hormone levels. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Cycle outcomes, including oocyte yield, number of mature oocytes, total gonadotropin dose, and peak E2 levels. RESULT(S): The mean number of oocytes retrieved in the transgender group was 19.9 ± 8.7 compared with 15.9 ± 9.6 in the cisgender group. Peak E2 levels were the same between the two groups. The total dose of gonadotropins used was higher in the transgender group compared with the cisgender group (3,892 IU vs. 2,599 IU). Of the 26 patients, 16 performed oocyte banking only. Seven couples had fresh or frozen transfers, with all achieving live births. CONCLUSION(S): This is the first study of this size investigating ART outcomes in female-to-male transgender patients. The findings may serve to reassure transgender patients and their care providers that outcomes can be excellent even if testosterone therapy has already been initiated. Further investigation needs to be performed on the generalizability of these findings, and whether similar results can be achieved without stopping testosterone therapy.

RNA-seq as a tool for evaluating human embryo competence.

The majority of embryos created through in vitro fertilization (IVF) do not implant. It seems plausible that rates of implantation would improve if we had a better understanding of molecular factors affecting embryo competence. Currently, the process of selecting an embryo for uterine transfer uses an ad hoc combination of morphological criteria, the kinetics of development, and genetic testing for aneuploidy. However, no single criterion can ensure selection of a viable embryo. In contrast, RNA-sequencing (RNA-seq) of embryos could yield high-dimensional data, which may provide additional insight and illuminate the discrepancies among current selection criteria. Recent advances enabling the production of RNA-seq libraries from single cells have facilitated the application of this technique to the study of transcriptional events in early human development. However, these studies have not assessed the quality of their constituent embryos relative to commonly used embryological criteria. Here, we perform proof-of-principle advancement to embryo selection procedures by generating RNA-seq libraries from a trophectoderm biopsy as well as the remaining whole embryo. We combine state-of-the-art embryological methods with low-input RNA-seq to develop the first transcriptome-wide approach for assessing embryo competence. Specifically, we show the capacity of RNA-seq as a promising tool in preimplantation screening by showing that biopsies of an embryo can capture valuable information available in the whole embryo from which they are derived. Furthermore, we show that this technique can be used to generate a RNA-based digital karyotype and to identify candidate competence-associated genes. Together, these data establish the foundation for a future RNA-based diagnostic in IVF.

Risk of ischemic placental disease is increased following in vitro fertilization with oocyte donation: a retrospective cohort study.

PURPOSE: Assess the risk of ischemic placental disease (IPD) among in vitro fertilization (IVF; donor and autologous) pregnancies compared with non-IVF pregnancies. METHODS: This was a retrospective cohort study of deliveries from 2000 to 2015 at a tertiary hospital. The exposures, donor, and autologous IVF, were compared with non-IVF pregnancies and donor IVF pregnancies were also compared with autologous IVF pregnancies. The outcome was IPD (preeclampsia, placental abruption, small for gestational age (SGA), or intrauterine fetal demise due to placental insufficiency). We defined SGA as birthweight < 10th percentiles for gestational age and sex. A secondary analysis restricted SGA to < 3rd percentile. RESULTS: Of 69,084 deliveries in this cohort, 262 resulted from donor IVF and 3,501 from autologous IVF. Compared with non-IVF pregnancies, IPD was more common among donor IVF pregnancies (risk ratio (RR) = 2.9; 95% CI 2.5-3.4) and autologous IVF pregnancies (RR = 2.0; 95% CI 1.9-2.1), adjusted for age and parity. IVF pregnancies were more likely to be complicated by preeclampsia (donor RR = 3.8; 95% CI 2.8-5.0 and autologous RR = 2.2; 95% CI 2.0-2.5, adjusted for age, parity, and marital status), placental abruption (donor RR = 3.8; 95% CI 2.1-6.7 and autologous RR = 2.5; 95% CI 2.1-3.1, adjusted for age), and SGA (donor RR = 2.7; 95% CI 2.1-3.4 and autologous RR = 2.0; 95% CI 1.9-2.2, adjusted for age and parity). Results were similar when restricting SGA to < 3rd percentile. CONCLUSION: Pregnancies conceived using donor IVF and autologous IVF were at higher risk of IPD and its associated conditions than non-IVF pregnancies and associations were consistently stronger for donor IVF pregnancies.

Risk of ischemic placental disease in fresh and frozen embryo transfer cycles.

OBJECTIVES: To evaluate the association of fresh and frozen embryo transfer with the development of ischemic placental disease (IPD), hypothesizing that differences in implantation environment affect placentation and thus pregnancy outcomes. DESIGN: We performed a secondary analysis of a retrospective cohort study of deliveries linked to IVF cycles. SETTING: Tertiary hospital and infertility treatment center. PATIENT(S): We included all women who underwent an autologous IVF cycle and had a live-born infant or an intrauterine fetal demise (IUFD). We excluded women less than 18 years of age. INTERVENTION(S): We compared pregnancies resulting from frozen embryo transfer (frozen) cycles with those resulting from fresh embryo transfer (fresh) cycles. MAIN OUTCOME MEASURE(S): The primary outcome was a composite outcome of IPD or IUFD due to placental insufficiency. Ischemic placental disease included pre-eclampsia, placental abruption, and small for gestational age (SGA). We calculated risk ratios (RRs) and 95% confidence intervals (CIs). RESULT(S): Compared with fresh cycles, frozen cycles had a lower risk of IPD or IUFD from placental insufficiency (RR 0.75, 95% CI 0.59-0.97). Frozen cycles also conferred a lower risk of SGA than fresh cycles (RR 0.58, 95% CI 0.41-0.81). Risks of pre-eclampsia (RR 1.3, 95% CI 0.84-1.9) and abruption (RR 1.2, 95% CI 0.56-2.4) were similar. CONCLUSION(S): There was a lower risk of IPD among frozen cycles compared with fresh cycles. This association was largely driven by lower risk of SGA among frozen cycles.

To test or not to test? A framework for counselling patients on preimplantation genetic testing for aneuploidy (PGT-A).

STUDY QUESTION: What is the treatment path and cumulative live birth (CLB) rate from a single oocyte retrieval of patients who intend to pursue PGT-A at the start of an IVF cycle compared to matched controls? SUMMARY ANSWER: The choice of PGT-A at the start of the first IVF cycle decreases the CLB per oocyte retrieval for patients <38 years of age, however patients ≥38 years of age benefit significantly per embryo transfer (ET) when live birth (LB) is evaluated. WHAT IS KNOWN ALREADY: PGT-A has been shown to reduce the practice of transferring multiple embryos and to confer a higher live birth rate per transfer. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study from December 2014 to September 2016, involving 600 patients: those intending PGT-A for their first IVF cycle (N = 300) and their matched controls. Post-hoc power calculations (alpha of 0.05, power of 0.80) indicated that our study was powered adequately to demonstrate significant differences in CLB per retrieval and LB per transfer. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was performed at a large academically affiliated infertility practice where approximately 80% of patients have insurance coverage for fertility care. Patients were identified through electronic medical records, and those who intended to pursue PGT-A at the start of stimulation were assessed. Patients were matched by age, time of oocyte retrieval and oocyte yield to the same number of controls. CLB outcomes per single retrieval, including the fresh and frozen transfers arising from the initial stimulation cycle, were calculated. MAIN RESULTS AND THE ROLE OF CHANCE: PGT-A was not beneficial when CLB rate was assessed per retrieval, however its benefits were significant when LB rate was assessed per transfer. First cycle, <38 year-old patients who intended to have PGT-A had a significantly (P < 0.001) lower CLB rate per oocyte retrieval compared to controls (49.4% vs. 69.1%). Conversely, patients ≥ 38 years in the PGT-A group had similar CLB rates compared to controls per oocyte retrieval, while LB rates per transfer were doubled compared to controls (62.1% vs. 31.7%; P < 0.001). Of the first-cycle PGT-A and control patients, 25.3% and 2.3% failed to achieve a transfer, respectively. LIMITATIONS, REASONS FOR CAUTION: This is not a true intention-to-treat study, due to its retrospective nature. Additionally, the number of patients with two or more previous miscarriages was significantly greater in the PGT-A group as compared to controls, however a sub-analysis showed that this failed to impact outcomes. WIDER IMPLICATIONS OF THE FINDINGS: The findings indicate that PGT-A may be detrimental for those <38 years old undergoing their first IVF cycle. PGT-A has the greatest clinical impact when a transfer is achieved in the ≥38 years old population. This study evaluates the typical treatment path following a patient's choice to pursue PGT-A at the cycle start, and can be used as a guide for counselling patients in relation to age and cycle number. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Cost Analysis of Following Up Incomplete Low-Risk Fetal Anatomy Ultrasounds.

OBJECTIVES: To examine the clinical utility and cost of follow-up ultrasounds performed as a result of suboptimal views at the time of initial second-trimester ultrasound in a cohort of low-risk pregnant women. METHODS: We conducted a retrospective cohort study of women at low risk for fetal structural anomalies who had second-trimester ultrasounds at 16 to less than 24 weeks of gestation from 2011 to 2013. We determined the probability of women having follow-up ultrasounds as a result of suboptimal views at the time of the initial second-trimester ultrasound, and calculated the probability of detecting an anomaly on follow-up ultrasound. These probabilities were used to estimate the national cost of our current ultrasound practice, and the cost to identify one fetal anomaly on follow-up ultrasound. RESULTS: During the study period, 1,752 women met inclusion criteria. Four fetuses (0.23% [95% CI 0.06-0.58]) were found to have anomalies at the initial ultrasound. Because of suboptimal views, 205 women (11.7%) returned for a follow-up ultrasound, and one (0.49% [95% CI 0.01-2.7]) anomaly was detected. Two women (0.11%) still had suboptimal views and returned for an additional follow-up ultrasound, with no anomalies detected. When the incidence of incomplete ultrasounds was applied to a similar low-risk national cohort, the annual cost of these follow-up scans was estimated at $85,457,160. In our cohort, the cost to detect an anomaly on follow-up ultrasound was approximately $55,000. CONCLUSIONS: The clinical yield of performing follow-up ultrasounds because of suboptimal views on low-risk second-trimester ultrasounds is low. Since so few fetal abnormalities were identified on follow-up scans, this added cost and patient burden may not be warranted.

How many oocytes are optimal to achieve multiple live births with one stimulation cycle? The one-and-done approach.

OBJECTIVE: To study how many infertility patients would complete an average-sized family (achieve ≥2 live births) after a single, complete in vitro fertilization (IVF) cycle. DESIGN: A retrospective cohort study. SETTING: University-affiliated private infertility practice. PATIENT(S): Women undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The outcome of 1 or ≥2 live births after a single retrieval cycle, followed by use of all embryos in subsequent frozen cycles in relation to oocyte number. RESULT(S): The pregnancy rate was statistically significantly higher when ≥15 oocytes were retrieved (289 of 699, 41.3%) than <15 oocytes (518 of 1,419, 36.5%). When investigating the outcome of ≥2 live births and assuming that all remaining frozen embryos were used, we found that 498 of 2,226 (22.4%) patients would achieve ≥2 live births. We performed multivariate analysis, and the area under the receiver operating characteristic curve for the model was 0.802. When controlling for multiple factors we found that as the number of oocytes retrieved increased, the chance of at least two live births increased, with odds ratio 1.08 (8% live birth increase per additional oocyte). CONCLUSION(S): We demonstrate that one fresh cycle with high oocyte yield is an optimal way to plan IVF treatment. With modern cryopreservation methods, the concept of "one-and-done" could safely achieve ≥2 live births with just one stimulation cycle in almost a quarter of our patients.

Hydronephrosis: A Rare Presentation of Uterine Didelphys with Obstructed Hemivagina and Ipsilateral Renal Anomaly.

BACKGROUND: Obstructed hemivagina and ipsilateral renal anomaly syndrome is a Müllerian duct anomaly characterized by uterine didelphys, obstructed hemivagina, and ipsilateral renal anomalies. CASE: A 12-year-old girl with a history of right renal agenesis presented to the emergency department with abdominal pain, dysuria, and urinary retention. Imaging identified a uterine didelphys with a large obstructed right hemivagina compressing the left ureter, causing hydronephrosis. She underwent vaginal septum resection for curative treatment. SUMMARY AND CONCLUSION: In female patients who present with abdominal pain and a history of renal abnormalities, obstructed hemivagina and ipsilateral renal anomaly syndrome must be considered in the differential diagnosis. This consideration is important in preventing complications such as hydronephrosis seen in this patient.

Fertility Preservation for Prepubertal Girls: Update and Current Challenges.

With increasing rates of diagnosis of childhood cancers and the evolution of more effective treatment options resulting in prolonged life spans, fertility preservation counseling is an integral component of the discussion at the time of diagnosis of childhood cancers. The primary fertility preservation option that exists for prepubertal girls is ovarian tissue cryopreservation. Although ovarian tissue cryopreservation is still considered to be experimental in nature, live births have resulted from orthotopic tissue transplantation. Fertility preservation should be offered to all prepubertal girls at high-risk for premature ovarian failure as a result of gonadotoxic treatment. Ethical and legal questions surrounding these issues must be considered as more and more pediatric patients pursue fertility preservation.