Early embryo development anomalies identified by time-lapse system: prevalence and impacting factors.

RESEARCH QUESTION: What is the prevalence of embryo abnormal early cleavage (ACL) identified by time lapse and factors related to patients and treatment that explain ACL occurrence? DESIGN: A single-centre, retrospective cohort study. Data were collected on all IVF cycles for which embryos were observed in the EmbryoScope® between December 2015 and August 2017. Only diploid zygotes cleaved on day 2 were included. The study included 318 cycles (250 couples and 1343 embryos). Embryo videos were retrospectively analysed for ACL. The prevalence of each type of ACL was recorded. The influence of clinical factors (whether they were intrinsic to patients or specific to IVF treatment) on ACL occurrence was analysed in multivariate multilevel mixed-effect logistic regression analysis. RESULTS: A high prevalence of ACL was observed: 37.6% (505/1343) of embryos presented at least one ACL, 22.8% (306/1343) a trichotomous mitosis, 25.8% (347/1343) a rapid cleavage, 6.7% (90/1343) a cell fusion and two or more ACL (16.1%). Part of the variation (12-25%) in ACL occurrence could be explained by embryo origin. Trichotomous mitosis and two or more ACL phenotypes were less likely to occur in women with endometriosis or tubal pathology and tubal pathology alone, respectively. No factor related to IVF cycles was found to be statistically associated with ACL occurrence. CONCLUSIONS: Our findings emphasize the importance of considering embryo origin when interpreting studies focusing on embryo characteristics and factors that could affect their quality. The present study is limited by a small sample size of known embryo implantations and monocentric criterion.

[Impact of geographical origin on IVF results: A monocentric observational French cohort study comparing 3 populations: Europe, Maghreb and Sub-Saharan Africa]. / Impact de l'origine géographique sur les résultats en FIV : Une étude de cohorte française observationnelle monocentrique comparant 3 populations : Europe, Maghreb et Afrique Subsaharienne.

OBJECTIVE: Many studies in the literature have found an association between geographic origin and poorer IVF outcomes in African American and Asian minority populations compared with Caucasian populations. The limitations of these studies are multiple (inconsistencies in the characterization of ethnic groups, mostly multicenter studies with large variability in success rates between centers, minorities having more limited and delayed access to care). Thus, socioeconomic status may have been an important bias in judging environmental or "genetic" factors. The objective of our study is to determine whether geographic origin would influence IVF response and outcomes in a French university hospital center with equal access to care. MATERIAL AND METHODS: This was a retrospective single-center observational study from January 2013 to January 2020 comparing IVF response in 3 populations of similar size at our Medically Assisted Reproduction center, with all charges covered by Medicare. The primary objective was ovarian response to IVF, and the secondary objectives were clinical pregnancy rate and live birth rate per cycle started. RESULTS: We analyzed 1669 cycles of first IVF attempt in women from Europe (525), Sub-Saharan Africa (649) and Maghreb (495). The SSA and Maghrebi women had a higher BMI. SSA women were more often affected by tubal or uterine infertility, HIV or HBV infection, and were less often nulliparous. The indication of male infertility was more frequent in Maghrebi women with a higher ICSI rate. There was no significant difference in the duration of stimulation, endometrial thickness at induction, number of oocytes collected, fertilization rate, number of embryos transferred and frozen. Nevertheless, the cancellation rate was higher in SSA and Maghrebi women and the total dose of gonadotropins was higher in SSA. No significant difference was found between Maghrebi and European women on IVF outcomes except for a lower number of total embryos in Maghrebi women (3.33 vs. 4.13 on average, P<0.001). The SSA had a lower rate of mature oocytes per puncture (66 % vs. 73 %, P<0.001), a lower number of total embryos per puncture (3.56 vs. 4.13 on average, P<0.016), a lower rate of clinical pregnancies per cycle (11.7% vs. 20.4%, P<0.001), a lower rate of live births per cycle (6.9% vs. 15.2%, P<0.001). CONCLUSION: There was no significant difference between European and Maghrebi women at the end of IVF, but the results were lower for those from SSA.

Higher live birth rate with stimulated rather than artificial cycle for frozen-thawed embryo transfer.

OBJECTIVE: To study which endometrial preparation allows a better ongoing pregnancy rates (OPR) and live birth rate (LBR) after frozen-thawed embryo transfer (FET) between mild gonadotropin ovarian stimulation (OS) and artificial cycles (AC). STUDY DESIGN: Retrospective follow-up study including all FET performed in one fertility center from 2013 to 2016. In the OS group, gonadotropins were followed by r-hCG triggering. Vaginal micronized progesterone (200 mg/day) was given systematically. In the AC group, estradiol (E2) was started on Day 1. Vaginal micronized progesterone (600 mg/d) was added to E2 for 12 weeks. Data were analyzed using a multiple regression model. RESULTS: Among 1021 FETs, 35% underwent OS preparation, 65% had an AC. As expected, patients in the AC group suffered more from endometriosis (18.5% vs. 12.9%; p = .021) and polycystic ovarian syndrome (21.7% vs. 10.9%; p < .0001) than patients in the OS group. There was no difference between groups with respect to endometrial thickness, number of embryos transferred, development stage at FET, cryopreservation technique. Despite a similar clinical pregnancy rate (CPR) (24.4% vs. 20.8%; p = .189), the OPR was significantly higher in the OS than in the AC group (17.9% vs. 11%; p = .002), leading to an increased LBR (17.1% vs. 9.8%; p < .001). After adjusting for parameters usually linked to early pregnancy losses or potential bias (patient age at freezing, smoking status, PCOS, endometriosis, rank of transfer and previous miscarriages), the results remained significant. CONCLUSION: Despite a similar CPR, LBR was significantly higher with mild OS than with the AC preparation, even after adjusting for potential confounders. In light of these results, the first-line endometrial preparation could be OS instead of an AC. In an AC, a potential defect of the luteal phase may exist, treatment could be optimized to avoid pregnancy losses. A randomized controlled trial should be undertaken to assess the role of OS and ACs in FET.

Poor Compliance to Hormone Therapy and Decreased Bone Mineral Density in Women with Premature Ovarian Insufficiency.

Premature ovarian insufficiency leads to through infertility and estrogen deficiency. Optimal management encompasses estrogen replacement therapy. Long-term outcome of women with POI is not known. We design a study to evaluate the medical care, hormone replacement therapy compliance and bone mineral density (BMD) in POI women with at least a five-year follow-up after the first evaluation. One hundred and sixty-two patients (37.3±8.0 years) were evaluated (follow-up 7.9±2.8 years). Sixty-nine patients (42.6%) had stopped their hormone replacement therapy (HRT) for at least one year during the follow up period. BMD determination at initial evaluation and at follow-up visit was completed in 92 patients. At first evaluation, 28 patients (30%) had osteopenia and 7 (8%) had osteoporosis. At follow up, 31 women (34%) had BMD impairment with osteopenia in 61% and osteoporosis in 5%. In univariate analysis and multivariate analysis, there was a significant loss of femoral BMD in women who had stopped their HRT for over a year. In conclusion, this first study concerning long-term follow-up of POI patients shows the poor compliance to their HRT, despite its importance in the prevention of bone demineralization. This study reinforces the need for follow up and specific care for POI women.

Resumption of ovarian function and pregnancies in 358 patients with premature ovarian failure.

CONTEXT: Resumption of ovarian activity and spontaneous pregnancies are described in patients with premature ovarian failure (POF), but there is a lack of data concerning the prevalence of and predictive factors for these phenomena. OBJECTIVE: The aim of the study was to determine both the prevalence of and predictive factors for spontaneous resumption of ovarian function in POF patients. DESIGN AND SETTING: A mixed retrospective and prospective study was performed at a referral center for reproductive endocrinology. PATIENTS: A total of 358 consecutive POF patients were followed from 1997 to 2010 in our center. MAIN OUTCOMES MEASURES: The cumulative incidence of resumption of ovarian function was determined, and predictive factors were identified by univariate and multivariate analysis. RESULTS: Of 358 patients with idiopathic POF, 86 (24%) patients presented features indicating resumption of ovarian function, and in 77 cases (88%) within 1 yr of diagnosis. Twenty-one spontaneous pregnancies (16 births, five miscarriages) occurred in 15 (4.4%) patients. Multivariate analysis (Cox model) showed that a familial history of POF, secondary amenorrhea, presence of follicles at ultrasound, and inhibin B and estradiol levels were significantly predictive of resumption of ovarian function (P < 0.01), whereas association with an autoimmune disease, anti-mullerian hormone level, the presence of follicles on biopsy, and/or genetic abnormalities did not appear predictive. We created a predictive score for resumption of ovarian function comprising age at diagnosis, presence of follicles at ultrasound, and inhibin B level. CONCLUSION: Intermittent ovarian activity in patients with POF is not a rare phenomenon. The predictive score described in this study may help us to identify POF patients most likely to recover intermittent ovarian function.