A history of recurrent pregnancy loss is associated with increased perinatal complications, but not necessarily a longer birth interval: a population study spanning 18 years.

STUDY QUESTION: Is there a difference in the time interval between the first and second live births among individuals with and without recurrent pregnancy loss (RPL)? SUMMARY ANSWER: Primary RPL (two or more pregnancy losses before the first live birth) is associated with a shorter time interval between the first and second live births compared with individuals without RPL, but this association is reversed in patients with secondary RPL (RPL patients with no or one pregnancy loss before the first live birth). WHAT IS KNOWN ALREADY: There is limited information regarding the ability to have more than one child for patients with RPL. Previous studies have investigated the time to live birth and the live birth rate from the initial presentation to clinical providers. Most of the previous studies have included only patients treated at specialized RPL clinics and thus may be limited by selection bias, including patients with a more severe condition. STUDY DESIGN, SIZE, DURATION: We conducted a population-based retrospective cohort study of 184 241 participants who delivered in British Columbia, Canada, and had at least two recorded live births between 2000 and 2018. The aim was to study the differences in the time interval between the first and second live births and the prevalence of pregnancy complications in patients with and without RPL. Additionally, 198 319 individuals with their first live birth between 2000 and 2010 were studied to evaluate cumulative second live birth rates. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among individuals with at least two recorded live births between 2000 and 2018, 12 321 patients with RPL and 171 920 participants without RPL were included. RPL was defined as at least two pregnancy losses before 20 weeks gestation. Patients with primary RPL had at least two pregnancy losses occurring before the first live birth, while patients with secondary RPL had no or one pregnancy loss before the first live birth. We compared the time interval from the first to second live birth in patients with primary RPL, those with secondary RPL, and participants without RPL using generalized additive models to allow for a non-linear relationship between maternal age and time interval between first and second live births. We also compared prevalence of pregnancy complications at the first and second live births between the groups using non-parametric Kruskal-Wallis H test and Fisher's exact test for continuous and categorical variables, respectively. We assessed the cumulative second live birth rates in patients with primary RPL and those without RPL, among participants who had their first live birth between 2000 and 2010. Cox proportional hazards model was used to estimate and compare hazard ratios between the two groups using a stratified modelling approach. MAIN RESULTS AND THE ROLE OF CHANCE: The adjusted time interval between the first and second live births was the longest in patients with secondary RPL, followed by individuals without RPL, and the shortest time interval was observed in patients with primary RPL: 4.34 years (95% CI: 4.09-4.58), 3.20 years (95% CI: 3.00-3.40), and 3.05 years (95% CI: 2.79-3.32). A higher frequency of pregnancy losses was associated with an increased time interval between the first and second live births. The prevalence of pregnancy complications at the first and second live births, including gestational diabetes, hypertensive disorder of pregnancy, preterm birth, and multiple gestations was significantly higher in patients with primary RPL compared with those without RPL. The cumulative second live birth rate was significantly lower in patients with primary RPL compared with individuals without RPL. LIMITATIONS, REASONS FOR CAUTION: This study may be limited by its retrospective nature. Although we adjusted for multiple potential confounders, there may be residual confounding due to a lack of information about pregnancy intentions and other factors, including unreported pregnancy losses. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study provide information that will help clinicians in the counselling of RPL patients who desire a second child. STUDY FUNDING/COMPETING INTEREST(S): This study was supported in part by a grant from the Canadian Institutes of Health Research (CIHR): Reference Number W11-179912. M.A.B. reports research grants from CIHR and Ferring Pharmaceutical. He is also on the advisory board for AbbVie, Pfizer, and Baxter. The other authors report no conflict of interest. TRIAL REGISTRATION NUMBER: NCT04360564.

Diagnosis and Management of an Unusual Cyst 3 Years After Sacrocolpopexy.

BACKGROUND: Peritoneal inclusion cysts (PICs) are uncommon tumours that can pose diagnostic challenges. This report describes an unusual etiology and management of recurrent pelvic organ prolapse. CASE: A 48-year-old premenopausal woman presented with recurrent prolapse and urinary frequency after total abdominal hysterectomy and synthetic mesh sacrocolpopexy. On examination, a stage II rectoenterocele was noted. Her post-void residual was 760 mL as measured by bladder scanner, discrepant with in-and-out catheterization. Pelvic ultrasound revealed a 19-cm cystic pelvic mass. At laparoscopy a PIC was identified, and cystectomy, uterosacral plication, and Moschcowitz culdoplasty were performed. Complete symptom resolution was documented at 4 weeks and 3 months postoperatively. CONCLUSION: PICs should be included in the differential diagnosis of recurrent prolapse. Prolapse symptoms attributable to PICs can be treated with laparoscopic cystectomy.

Case report: an identical twin with Sertoli-Leydig cell tumor.

Our report details the workup and management of a 43-year-old woman with an identical twin who presented with 2 years of virilization and secondary amenorrhea. Serum total testosterone was elevated. An MRI did not identify adnexal or adrenal pathology. Subsequent ovarian vein sampling demonstrated unilateral testosterone elevation. The patient underwent laparoscopic unilateral oophorectomy resulting in the diagnosis of Sertoli-Leydig cell tumor (SLCT). Although SLCT is a rare sex-cord ovarian tumor, it is associated with endometrial hyperplasia and malignancy. Our goals are to review the workup of androgen-secreting tumors and discuss the clinical importance of the DICER1 mutation in the context of SLCT. In this case, an identical twin underwent DICER1 testing which was one of the essential steps in her clinical management.

Peak Serum Estradiol Level During Controlled Ovarian Stimulation Is not Associated with Lower Levels of Pregnancy-Associated Plasma Protein-A or Small for Gestational Age Infants: A Cohort Study.

OBJECTIVE: During controlled ovarian stimulation in IVF, supraphysiologic levels of estradiol (E2) have been associated with poor placentation and adverse pregnancy outcomes. This study aimed to investigate whether high peak E2 on the day of human chorionic gonadotropin trigger is associated with low pregnancy-associated plasma protein-A (PAPP-A) and adverse perinatal outcomes. METHODS: We performed a retrospective cohort study at a private, university-affiliated fertility centre in Vancouver, BC. We enrolled 216 patients with a singleton pregnancy after fresh embryo transfer who also underwent first trimester screening. Adverse perinatal outcomes were collected from a local registry and included preterm birth, hypertension in pregnancy, antepartum hemorrhage, intrauterine growth restriction, SGA, stillbirth, admission to the NICU, and neonatal death. RESULTS: High serum E2 (≥13 035 pmol/L) at controlled ovarian stimulation was not correlated with low PAPP-A (<0.4 multiples of the median) at first trimester screening (P = 0.46). When each adverse outcome was analysed separately, there was no association between high E2 and any of the outcomes (P > 0.05 for all). High peak E2 was not associated with a total composite of maternal and neonatal adverse birth outcomes (P = 0.30). CONCLUSION: Our results do not support the theory that high E2 at fresh embryo transfer impedes placentation. We found no association between peak E2 and low PAPP-A levels or adverse pregnancy outcomes.

Medical students' self-reported preparedness and attitudes in providing care to ethnic minorities.

BACKGROUND: To assess medical students' self-reported preparedness to provide care to ethnic minorities, factors that influence preparedness, and attitudes toward cultural competency training. METHODS: A cross-sectional study, which invited University of British Columbia medical students to participate in a survey on student demographics, knowledge and awareness, preparedness and willingness, and personal attitudes. Of 1024, eligible, 301 students consented to study. RESULTS: Students across all year levels felt significantly less ready to provide care for non-English speaking Chinese patients compared to "any" patients. Proficiency in working with interpreters was correlated with readiness, OR 4.447 (1.606-12.315) along with 3rd and 4th year level in medical school, OR 3.550 (1.378-9.141) and 4.424 (1.577-12.415), respectively. Over 80% of respondents reported interest in learning more about the barriers and possible ways of overcoming them. CONCLUSIONS: More opportunities for cultural competency training in the medical curriculum are warranted and would be welcomed by the students.

The use of combined hormonal contraceptive for in-vitro fertilization cycle priming is not associated with decreased pregnancy rate in frozen embryo transfer cycles: a cohort study.

BACKGROUND: The objectives of this study are to evaluate the cycle outcomes from IVF treatment preceded by oral contraceptive pills (OCP) priming compared to estradiol pretreatment and to determine if there is a role for OCP priming for those undergoing frozen embryo transfers. METHODS: The study took place at a university-affiliated fertility center in Canada. The study included in-vitro fertilization (IVF) antagonist cycles from Jan 2016 to Jun 2019. Those with protocol deviation or treatment cancellation were excluded. RESULTS: There were 2237 cycles by 1958 patients; 27% of cycles utilized OCP priming. The average age in the OCP group was 34 years old compared to 36.5 in the estradiol group (P<0.01). AMH was reported in 43% of patients and was 3.7ng/mL in the OCP group versus 2.2 ng/mL in the estradiol group (P<0.01). The number of oocytes (15.2 vs. 12.5) and number of blastocysts (4.6 vs. 3.3) were higher in the OCP group (P all <0.01). After adjusting for age and AMH with linear regression for the 978 cycles with recorded AMH (24% with OCP prime), a significantly higher number of oocytes (13.8 vs. 11.9, P=0.002) was still noted in the OCP group. There were 866 euploid embryo transfer cycles (28% with OCP prime). There were no significant differences in implantation (77% vs. 76%) or ongoing pregnancy rates (56% vs. 54%) between those who had a frozen embryo transfer after OCP primed compared to estradiol primed stimulation cycles (P all >0.6). CONCLUSIONS: There were no differences in pregnancy outcomes from euploid frozen blastocyst transfers after OCP primed antagonist cycles compared to estradiol pretreatment. In fact, the use of OCP pretreatment was associated with increased oocyte yield, keeping in mind demographic differences with the OCP pretreatment group being younger with higher anti-Müllerian hormone and a higher prevalence of PCOS. Thus, OCP priming should still be considered in specific populations, such as those with oligo-ovulation or adequate ovarian reserve.

Fertility preservation in a transgender man without prolonged discontinuation of testosterone: a case report and literature review.

OBJECTIVE: To study the feasibility of fertility preservation in a transgender man without an extended period of androgen cessation. DESIGN: Report of a foundational case of oocyte cryopreservation in a transgender man without stopping testosterone therapy before controlled ovarian stimulation. We performed a literature review, identifying five publications on oocyte cryopreservation outcomes in transgender men on testosterone. SETTING: A university-affiliated fertility clinic in Canada. PATIENTS: A 28-year-old transgender man taking testosterone for 3 years requesting oocyte cryopreservation before gender-affirming surgery. He desired to proceed without stopping testosterone. Pretreatment antimüllerian hormone level was 1.89 ng/mL. The patient's consent was obtained for written publication. INTERVENTIONS: Testosterone was stopped for only three doses (immediately before and during ovarian stimulation). A standard antagonist protocol was used with letrozole to minimize estrogenic side effects. MAIN OUTCOME MEASURES: Number of oocytes retrieved and days off testosterone. RESULTS: Thirteen oocytes were retrieved; 11 were mature and vitrified. The total time off testosterone was 24 days. In all prior publications, testosterone was stopped for 3-6 months. CONCLUSIONS: Transgender men have traditionally discontinued exogenous testosterone until the resumption of menses (≤6 months). This is known to be distressing. This is the first published case demonstrating the feasibility of ovarian stimulation without prolonged testosterone cessation in a transgender man. Future studies with a larger sample size should be performed to confirm these findings. The short duration off testosterone may improve patient's experiences, increase treatment acceptability, and decrease gender dysphoria for transgender men considering fertility preservation.

Anti-Müllerian hormone and embryo quality as determined by time-lapse imaging.

BACKGROUND: There is conflicting evidence as to whether serum anti-Mullerian hormone (AMH) is a biomarker of oocyte quality in addition to its known role in assessing ovarian reserve. This study aims to examine the relationship between AMH and embryo potential as assessed by time-lapse imaging (TLI). METHODS: A total of 106 embryos from 67 patients were included in the study. All subjects were women with recorded pre-treatment AMH levels who underwent in vitro fertilization using a TLI embryo incubator. Exclusion criteria included cases of donor oocytes, rescue-ICSI, and >2 embryos transferred. Individual time measures, presence of multinucleation (MN), and composite TLI score were analyzed in relation to patient AMH. Linear regression was used to model AMH among embryo TLI parameters while controlling for age as a continuous covariate. RESULTS: There was no statistically significant difference in the mean AMH levels between patients in the normal and abnormal time frames for CC2, S2, and T5. Similarly, there was no significant difference in AMH levels based on composite TLI score or presence/absence of multinucleation. The lack of association between AMH levels and embryo TLI variables persisted after controlling for age (Grade P=0.19, CC2 P=0.47, S2 P=0.52, t5 P=0.34, MN P=0.92). CONCLUSIONS: Serum AMH is not predictive of embryo quality as assessed by TLI standardized time intervals, composite score, and presence of MN. From a clinical perspective, these findings suggest that diminished ovarian reserve alone does not imply poorer quality of individual embryos.

Adverse perinatal outcomes associated with crown-rump length discrepancy in in vitro fertilization pregnancies.

OBJECTIVE(S): To determine whether an association exists between small crown-rump length (CRL) and adverse obstetrical outcomes in pregnancies conceived by IVF and to compare a CRL reference based on IVF pregnancies to a reference based on spontaneous pregnancies. DESIGN: Retrospective cohort study. CRL was classified as small by comparing it with the local university hospital maternal fetal medicine standard and the Monash IVF reference chart. SETTING: University-affiliated fertility center. PATIENT(S): Singleton pregnancies conceived by IVF with ultrasounds performed between 7+0 and 8+6 weeks of gestational age. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy loss, preterm birth, and low birth weight. RESULT(S): Included were 940 clinical pregnancies. The overall and CRL-discrepant miscarriage rates were 12.7% and 41%, respectively. When CRL was small, the maternal age-adjusted odds of miscarriage were 13.8 times higher (95% confidence interval [CI], 8.9-21.6). At age 30, small CRL was associated with a 30% risk of miscarriage, versus 61% at age 45. There was no association between small CRL and preterm birth or low birth weight. The sensitivity and specificity for predicting miscarriage from the optimal Monash cut point were 0.69 (95% CI, 0.61-0.77) and 0.84 (95% CI, 0.82-0.87), which were similar to those of the CRL reference based on spontaneous pregnancies. CONCLUSION(S): Small CRL in IVF pregnancy was strongly associated with miscarriage, especially in the context of advanced maternal age. Small CRL was not associated with preterm birth or low birth weight. A CRL reference based on IVF pregnancies was equivalent to the standard reference for predicting miscarriage.