Obstetric and Neonatal Outcomes After Transferring More Than One Embryo in Patients With Preimplantation Genetic Testing.

OBJECTIVE: To compare obstetric and neonatal outcomes after single embryo transfer (SET) compared with multiple embryo transfer (MET) from frozen-thawed transfer cycles of embryos that underwent preimplantation genetic testing for aneuploidies (PGT-A). METHODS: We conducted a retrospective cohort study from the SART CORS (Society for Assisted Reproductive Technology Clinic Outcome Reporting System) national database. Clinical and demographic data were obtained from the SART CORS database for all autologous and donor egg frozen-thawed transfer cycles of embryos that underwent PGT-A between 2014 and 2016, after excluding cycles that used frozen oocytes, fresh embryo transfer, and transfers of embryos from more than one stimulation cycle. Multivariable linear and log-binomial regression models were used to estimate the relative and absolute difference in live-birth rate, multiple pregnancy rate, gestational age at delivery, and birth weight between SET compared with MET. RESULTS: In total, 15,638 autologous egg transfer cycles and 944 donor egg transfer cycles were analyzed. Although the live-birth rate was higher with MET compared with SET in the autologous oocyte cycles (64.7% vs 53.2%, relative risk [RR] 1.24, 95% CI, 1.20-1.28), the multiple pregnancy rate was markedly greater (46.2% vs 1.4%, RR 32.56, 95% CI, 26.55-39.92). Donor oocyte cycles showed similar trends with an increased live-birth rate (62.0% vs 49.7%, RR 1.26, 95% CI, 1.11-1.46) and multiple pregnancy rate (54.0% vs 0.8%) seen with MET compared with SET. Preterm delivery rates and rates of low birth weight were significantly higher in MET compared with SET in both autologous and donor oocyte cycles and were also higher in the subanalysis of singleton deliveries that resulted from MET compared with SET. CONCLUSION: Despite some improvement in live-birth rate, nearly half of the pregnancies that resulted from MET of embryos that underwent PGT-A were multiples. Compared with SET, MET is associated with significantly higher rates of neonatal morbidity, including preterm delivery and low birth weight. The transfer of more than one embryo that underwent PGT-A should continue to be strongly discouraged, and patients should be counseled on the significant potential for adverse outcomes.

Validity Study of an End-of-Clerkship Oral Examination in Obstetrics and Gynecology.

OBJECTIVE: Surgical clerkships frequently include oral exams to assess students' ability to critically analyze data and utilize clinical judgment during common scenarios. Limited guidance exists for the interpretation of oral exam score validity, thus making improvements difficult to target. We examined the development, administration, and scoring of a clerkship oral exam from a validity evidence framework. DESIGN: This was a retrospective study of a third-year, end-of-clerkship oral exam in obstetrics and gynecology (OBGYN). Content, response process, internal structure, and relationship to other variables validity evidence was collected and evaluated for 5 versions of the oral exam. SETTING: Albert Einstein College of Medicine, Bronx, New York City. PARTICIPANTS: Participants were 186 third-year medical students who completed the OBGYN clerkship in the academic year 2020 to 2021. RESULTS: The average number of objectives assessed per oral exam version were uniform, but the distribution of questions per Bloom's level of cognition was uneven. Student scores on all questions regardless of Bloom's level of cognition were >87%, and reliability (Cronbach's alpha) of item scores varied from 0.58 to 0.74. There was a moderate, positive correlation (Spearman's rho) between the oral exam scores and national shelf exam scores (0.35). There were low correlations between oral exam scores and (a) clinical performance ratings (0.14) and (b) formal presentation scores (-0.19). CONCLUSIONS: This study provides an example of how to examine the validity of oral exam scores for targeted improvements. Further modifications are needed before using scores for high stakes decisions. The authors provide recommendations for additional sources of validity evidence to collect in order to better meet the goals of any surgical clerkship oral exam.

Adherence to embryo transfer guidelines in favorable-prognosis patients aged less than 35 years using autologous oocytes and in recipients using donor oocytes: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System study.

OBJECTIVE: To measure the consequences of nonadherence with the 2013 American Society for Reproductive Medicine elective single embryo transfer (eSET) guidelines for favorable-prognosis patients. DESIGN: Retrospective cohort. SETTING: In vitro fertilization clinics. PATIENT(S): A total of 28,311 fresh autologous, 2,500 frozen-thawed autologous, and 3,534 fresh oocyte-donor in vitro fertilization cycles in 2014-2016 at Society for Assisted Reproductive Technology-reporting centers. INTERVENTION(S): Patients aged <35 years or using donors aged <35 years underwent first blastocyst transfer. MAIN OUTCOME MEASURE(S): Singleton birth rate, gestational age at delivery, and birth weight were compared between the eSET and non-eSET groups using the chi-square or Fisher's exact test or t-tests. RESULT(S): Among fresh transfers, 15,643 (55%) underwent eSET. Live births after non-eSETs were less likely singletons (38.0% vs. 96.5%; adjusted relative risk [aRR], 0.56) and more likely complicated by preterm delivery (55.0% vs. 20.1%; aRR, 2.39) and low birth weight (<2,500 g) (40.1% vs. 10.6%; aRR, 3.4) compared with those after eSET. Among frozen-thawed transfers, 1,439 (58%) underwent eSET. Live births after non-eSETs were less likely singletons (41.9% vs. 95.2%; aRR, 0.69; 95% confidence interval, 0.66-0.73) and more likely complicated by preterm delivery (56.4% vs. 19.5%; aRR, 2.6; 95% confidence interval, 2.2-3.1) and low birth weight (38.0% vs. 8.9%; aRR, 3.9) compared with those after eSET. Among fresh donor oocyte transfers, 1,946 (55%) underwent eSET. Live births after non-eSETs were less likely singletons (31.3% vs. 97.3%; aRR, 0.48) and more likely complicated by preterm delivery (61.1% vs. 25.7%; aRR, 2.09) and low birth weight (44.3% vs. 11.7%; aRR, 3.39) compared with those after eSET. CONCLUSION(S): Nonadherence with transfer guidelines was associated with dramatically increased multiple pregnancies, preterm births, and low birth weights.

Early experience with universal SARS-CoV-2 testing in a New York-based reproductive endocrinology practice.

The SARS-CoV-2 pandemic peak around March 2020 led to temporary closures of most fertility clinics. Many clinics reopened but required universal SARS-CoV-2 screening. However, the rate of positive results and the necessity for such testing is unknown. We report here on early results from asingle-center academic NewYork fertility practice utilizing universal SARS-CoV-2 screening. This mixed prospective retrospective cohort included 164 patients who underwent at least one SARS-CoV-2 screening test for fertility treatment between May and July2020. Patients completed 1 to 3 nasopharyngeal SARS-CoV-2 tests per cycle and remained symptom-free to continue fertility treatments. SARS-CoV-2 test results, past results, history of Covid-19 infection, and patient/cycle characteristics were recorded and tabulated through October2020. Outcomes included positive SARS-CoV-2 RNA tests, rate of prior Covid-19 infections, and clinical courses of patients testing positive. Patients underwent 263 cycles entailing 460 total SARS-CoV-2 screening tests. Fifteen patients reported astrong prior clinical history of Covid-19. Six patients experienced apositive SARS-CoV-2 test (2.3% of all cycles). Among 77 cycles (n = 58 patients) entailing one SARS-CoV-2 test, 2 cases (2.6%) were noted. Among 173 cycles (n = 121 patients) entailing two SARS-CoV-2 tests, 4 cycles (2.3%) were noted. Zero (0%) of 13 cycles (n = 13 patients) entailing 3 SARS-CoV-2 tests were positive. All patients were cleared to resume treatment within one month. Overall, anew asymptomatic infection was identified in 2 cycles (0.8%), while 4 of the 6 positive SARS-CoV-2 tests were among patients with aprior history of Covid-19. 3 of 4 also had adocumented prior positive RNA test. Our data suggest that universal SARS-CoV-2 screening among fertility patients is feasible, with an approximately 2% positive rate per cycle among the patients of this study. Most positive patients had aprior remote infection, but their infectiousness while being screened remains unclear.Abbreviations: REI: reproductive endocrinology and infertility; IUI: intrauterine insemination; IVF: in vitro fertilization; sono: sonography; cryo: cryopreservation; FET: frozen embryo transfer.

Fertility preservation for cancer patients: treatment gaps and considerations in patients' choices.

PURPOSE: Women with cancer may desire fertility preservation (FP) prior to initiating cancer treatment, but undergoing FP may result in treatment delays. This study sought to determine whether such delays existed in our population and which factors were associated with patients' decision to proceed with FP. METHODS: This was a historical cohort study performed at Montefiore Medical Center's Institute for Reproductive Medicine and Health. Reproductive age women diagnosed with cancer and consulted for FP were included. The main outcome measure was the number of days between FP consultation and cancer treatment initiation. Factors associated with patients' decisions to proceed with FP were also analyzed. RESULTS: Thirty out of 51 women in our study underwent FP including embryo cryopreservation, oocyte cryopreservation, ovarian tissue cryopreservation (OTC), both oocyte and embryo cryopreservation, or GnRH agonist treatment. The majority of women who underwent FP chose embryo cryopreservation (36.7%), followed by oocyte cryopreservation (33.3%). Of the 20 patients with partners who underwent FP, 13 (65%) froze embryos. Only 4 of the 30 women who underwent FP had all, or a portion of their services, covered by insurance. The mean treatment delay was 18 days (p = 0.007), with a mean consultation to oncologic treatment gap of 23 ± 16.8 and 41.4 ± 25.9 days in the non-FP and FP groups, respectively. CONCLUSION: Women with cancer diagnosis who underwent FP prior to initiating cancer treatment experienced a statistically significant delay in initiating cancer treatment. However, the clinical significance of this finding is unknown since FP treatments have not been associated with increased recurrence or mortality.

Fertility Awareness Counseling for Adolescent Girls; Guiding Conception: The Right Time, Right Weight, and Right Way.

STUDY OBJECTIVE: To provide a detailed summary of fertility awareness counseling pearls for healthy teens and those with fertility-relevant comorbidities, and to assist providers in offering such counseling to adolescents and young adult women. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Comprehensive literature review of English-language studies relating to fertility in pediatric and adolescent female patients (ages 13-21 years), and evidence-based dialogue guide. RESULTS: The literature indicates that although adolescents are interested in discussing sexuality and reproduction, this is commonly overlooked during the standard office medical visit. As a result, adolescents often turn to less reliable sources and hold a variety of reproductive misconceptions and a sense of lack of control over future fertility. We found no studies that examined the routine provision of fertility awareness counseling with healthy adolescents. There are a multitude of specific gynecologic and medical conditions that have ramifications for fertility. We detail these comprehensively, and provide a dialogue guide to assist with fertility awareness counseling for the female adolescent, containing specific information and indications for referral. CONCLUSION: Providers caring for adolescent girls have the opportunity to enhance fertility awareness as part of a larger reproductive health conversation that adolescents desire, and from which they might benefit. Identifying potential future fertility issues, understanding age-related fertility decline, and aiding in health optimization before future conception might empower the adolescent to make informed reproductive decisions. We provide an algorithm to use with adolescents to discuss the "right time, right weight, right way" to pursue childbearing.

Near-peer role modeling: Can fourth-year medical students, recognized for their humanism, enhance reflection among second-year students in a physical diagnosis course?

INTRODUCTION: Humanism is cultivated through reflection and self-awareness. We aimed to employ fourth-year medical students, recognized for their humanism, to facilitate reflective sessions for second-year medical students with the intention of positively influencing reflective process toward humanistic development. METHODS/ANALYSIS: A total of 186 students were randomly assigned to one of three comparison arms: eight groups of eight students (64 students) were facilitated by a fourth-year student who was a Gold Humanism Honor Society member (GHHS); eight groups (64 students) by a volunteer non-GHHS student; and seven groups (58 students) were non-facilitated. Before sessions, second-year students set learning goals concerning interactions with patients; fourth-year students received training materials on facilitation. Groups met twice during their 10 clinical site visits. At the last session, students completed a reflective assignment on their goal progress. Comparative mixed method analyses were conducted among the three comparison arms on reflection (reflective score on in-session assignment) and session satisfaction (survey) in addition to a thematic analysis of responses on the in-session assignment. RESULTS: We found significant differences among all three comparison arms on students' reflective scores (p=0.0003) and satisfaction (p=0.0001). T-tests comparing GHHS- and non-GHHS-facilitated groups showed significantly higher mean reflective scores for GHHS-facilitated groups (p=0.033); there were no differences on session satisfaction. Thematic analysis of students' reflections showed attempts at self-examination, but lacked depth in addressing emotions. There was a common focus on achieving comfort and confidence in clinical skills performance. DISCUSSION/CONCLUSIONS: Near peers, recognized for their humanism, demonstrated significant influence in deepening medical students' reflections surrounding patient interactions or humanistic development. Overall, students preferred facilitated to non-facilitated peer feedback forums. This model holds promise for enhancing self-reflection in medical education, but needs further exploration to determine behavioral effects.

Actinomycosis pelvic abscess after in vitro fertilization.

OBJECTIVE: To report a case of pelvic actinomycosis presenting as large, multiloculated abscesses after an in vitro fertilization (IVF) cycle for male factor infertility. DESIGN: A case report and literature review. SETTING: University hospital. PATIENT(S): A 31-year-old nulligravid woman presenting with urinary retention, pelvic pain, and fever 6 days after transvaginal oocyte retrieval and an embryo transfer for male factor infertility. INTERVENTION(S): Intravenous and oral antimicrobial therapy, and computed tomography (CT)-guided drainage of pelvic abscesses. MAIN OUTCOME MEASURE(S): Clinical and radiologic resolution of symptoms and infection. RESULT(S): The CT scan revealed several large, multiloculated pelvic and tuboovarian abscesses. The patient defervesced after 6 days of intravenous antibiotics, but the pelvic pain did not improve. After CT-guided drainage of the pelvic abscesses, the patient's symptoms improved. The drained material was cultured, and the patient was diagnosed with pelvic actinomycosis tuboovarian abscesses, an infrequent cause of tuboovarian abscess and a rare complication of assisted reproductive technology (ART). The patient was switched from intravenous to oral antibiotics and discharged home. CONCLUSION(S): Pelvic Actinomyces israelii presenting as pelvic abscesses may occur as a rare complication of ART. Physicians should consider a diagnosis of tuboovarian abscess in a patient reporting fever and pelvic pain after IVF and embryo transfer.

Pituitary origin of persistently elevated human chorionic gonadotropin in a patient with gonadal failure.

OBJECTIVE: To report a case of persistently elevated low levels of hCG to increase awareness of pituitary origin of persistently elevated hCG in patients with gonadal failure. DESIGN: Case report and literature review. SETTING: Large university-affiliated infertility practice. PATIENT(S): A 16-year-old patient with primary amenorrhea, normal secondary sex characteristics, ovarian failure, and a 46,XY karyotype. Her past medical history was significant for focal segmental glomerulosclerosis, leading to a diagnosis of Frasier syndrome. INTERVENTION(S): At age 31 years, she desired pregnancy by oocyte donation and was found to have persistently elevated low levels of hCG (>35 mIU/mL). MAIN OUTCOME MEASURE(S): Pituitary hCG. RESULT(S): Both serum free ß-hCG and hyperglycosylated hCG were undetectable. Total serum hCG diluted appropriately was not blocked by blocking agent and was detected in the urine. Subsequent treatment with exogenous E(2), in preparation of a donor oocyte cycle, suppressed her hCG levels (down to 8 mIU/mL). These results indicated a pituitary source of the serum hCG. CONCLUSION(S): This report reinforces the need to consider pituitary hCG as the origin of persistently elevated hCG levels in patients with gonadal failure. Although levels of hCG <14 mIU/mL have been considered normal in postmenopausal women, our case suggests that patients with gonadal failure at younger ages might have a higher pituitary output of hCG.

Full-sibling embryos created by anonymous gamete donation in unrelated recipients.

OBJECTIVE: To report the rare occurrence of full-sibling embryos in unrelated women using independently chosen donor sperm and donor oocytes in two different cycles unintentionally created at our IVF program, and to discuss the concept of disclosure to the patients. DESIGN: Case report. SETTING: Academic IVF program. PATIENT(S): Two women independently undergoing donor recipient cycles with anonymous donor oocytes and donor sperm. INTERVENTION(S): Both women received oocytes from the same donor several months apart and then by coincidence selected the same anonymous sperm donor to create anonymous full-sibling embryos. MAIN OUTCOME MEASURE(S): Clinical pregnancy after donor-recipient IVF cycle. RESULT(S): Both women conceived using the same donor sperm and donor oocytes in independent cycles, resulting in simultaneous pregnancy of full siblings. CONCLUSION(S): As providers with the knowledge that anonymous full sibling embryos have been created, we may have an obligation to disclose this information to the patients.

Onset of ovulation after menarche in girls: a longitudinal study.

INTRODUCTION: Hypothalamic-pituitary axis maturity has been believed to be the rate-limiting step in the development of ovulatory menstrual cycles. We hypothesized that, given current nutritional conditions, hypothalamic-pituitary axis maturation would be relatively rapid in menarcheal girls. METHODS: Daily urine and menstrual records were collected for 2 yr each from 10 girls aged 11-13 yr at study entry. Urinary excretion of LH, FSH, estradiol (E1c), and progesterone (Pdg) metabolites was measured using established ELISAs. An objective algorithm detected rises of LH, FSH, E1c, and Pdg consistent with follicular maturation and/or ovulation. RESULTS: Nine of 10 girls enrolled into the study experienced the onset of menarche prior to or during the 2-yr collection period. LH and FSH surges, as well as small amplitude Pdg increments, were observed prior to menarche. Regular, ovulatory-appearing cycles with LH surges and gradually increasing and more sustained Pdg rises were observed over time after menarche, although duration of Pdg elevations remained shorter than in adult women (8.9 +/- 1.0 vs. 12.1 +/- 0.8 d, P = 0.043). E1c levels leading to LH/FSH surges were lower in perimenarcheal girls than adult controls, and bleeding episodes did not uniformly correlate with hormone patterns. Progressive increases in FSH and Pdg, but not LH or E1c, were observed in association with menarche. CONCLUSION: Mature hormone patterns are established within several months of and even prior to menarche in normal-weight perimenarcheal girls. Factors determining menstrual bleeding in perimenarcheal girls may not be solely dependent on reproductive hormones or the neuroendocrine axis.

Heterogeneity in endometrial expression of aromatase in polyp-bearing uteri.

BACKGROUND: Comparative assessment of expression of aromatase (CYP19A1) messenger RNA (mRNA) in pathological and non-pathological sites within the uterine cavity of mid reproductive age women diagnosed with endometrial polyp (EP). METHODS: We report a case series of seven premenopausal infertile women undergoing hyseroscopic removal of EP. Directed endometrial biopsies were collected from the EP (P), from the endometrium immediately adjoining the EP (A) and from a normal appearing site remote from the EP (R). Expression of CYP191A1 mRNA within the respective samples in each patient was evaluated by quantitative real-time PCR. Fold changes in the mRNA expression of CYP191A1 within the P versus the R and A endometrial sites were calculated to assess the hypothesis of a 'field effect' in the expression of aromatase within EP bearing endometria. RESULTS: Overall, similar mRNA expression of CYP191A1 gene was demonstrated between P and A endometrial samples. In only one of the seven patients, aromatase expression within P was enhanced by almost 4-fold compared with R (P = 0.14 for comparison with the difference in CYP19A1 expression in P versus R in the remainder of the patients). In contrast, in three of the seven patients, P demonstrated a marked (>1000-fold) under-expression in CYP191A1 mRNA levels compared with the R endometrium (P = 0.22). CONCLUSIONS: We herein provide evidence of heterogeneity in the expression of endometrial aromatase in premenopausal uteri bearing EPs. Our data suggest that an overexpression of endometrial aromatase may underlie pathogenesis of EP at least in a subset of cases.