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STUDY QUESTION Do obstetric outcomes and placental findings in pregnancies conceived with IVF vary according to embryo quality? SUMMARY ANSWER Pregnancies following the transfer of lower-quality embryos were associated with a higher rate of low-lying placentas and several adverse placental lesions. WHAT IS KNOWN ALREADY A few studies have shown reduced pregnancy and live births rates with poor-quality embryo transfer, yet with comparable obstetric outcomes. None of these studies included placental analysis. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of 641 deliveries of IVF attained pregnancies between 2009 and 2017 was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS Live singleton births after IVF with a single blastocyst transfer at a university-affiliated tertiary hospital were included. Excluded were cycles of oocyte recipients and IVM. We compared pregnancies following the transfer of a poor-quality blastocyst (poor-quality group) or a good-quality blastocyst (controls, good-quality group). During the study period, all placentas from complicated and uncomplicated pregnancies were sent to pathology. Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes, adjusted for diminished ovarian reserve, fresh versus frozen transfer, and neonatal gender (as indicated by univariable analysis). MAIN RESULTS AND THE ROLE OF CHANCE A total of 132 deliveries in the poor-quality group were compared to 509 controls. A diagnosis of diminished ovarian reserve was more common in the poor-quality group than in the control group (14.3% versus 5.5%, respectively, P LIMITATIONS, REASONS FOR CAUTION The study is limited by its retrospective design and the utilization of two grading systems during the study period. In addition, the sample size was limited to detect differences in outcomes of rarer occurrences. WIDER IMPLICATIONS OF THE FINDINGS The placental lesions demonstrated in our study imply an altered immunological response to the implantation of poor-quality embryos. Yet, these findings were not associated with additional adverse obstetric outcomes and merit reaffirmation in a larger cohort. Overall, the clinical findings of our study are reassuring to clinicians and patients for whom the transfer of a poor-quality embryo is necessary. STUDY FUNDING/COMPETING INTEREST(S) No external funding was obtained for this study. The authors declare no conflict of interest, TRIAL REGISTRATION NUMBER N/A.

To assess perinatal outcomes and placental findings in in vitro fertilization (IVF) patients with previous recurrent pregnancy loss (RPL).This was a retrospective cohort of live singleton births following IVF at a single university-affiliated center between 2009 and 2017. Outcomes were compared between patients with previous RPL, defined as two miscarriages (RPL group), and patients without RPL (control group). Placental examination was performed for all deliveries irrelevant of complications, and findings categorized according to the Amsterdam Placental Workshop Consensus.One hundred seventy-two deliveries of women with previous RPL (RPL group) were compared to 885 controls. Maternal age, 36.2 ± 4.2 vs. 35.4 ± 4.2 years, p = 0.02, and rate of uterine fibroids, 12.7% vs. 7.3%, p = 0.01, were higher in the RPL group. The rate of nulliparity was lower in the RPL group, 63.3% vs. 74.1%, p = 0.003. Unexplained infertility and diminished ovarian reserve were more common in the RPL group and male factor infertility in controls. There was a lower rate of fresh embryo transfer in the RPL group, 50.5% vs. 64.7%, p 0.001, and reduced endometrial thickness. Similar obstetric outcomes were noted in the groups after adjustment for confounders. Placental examinations were notable for lower placental thickness, β - 0.17 cm, 95%CI - 0.30-(- 0.0), a lower rate of velamentous cord insertion, aOR 0.44, 95%CI 0.20-0.95, and a higher rate of villous infarction, aOR 2.82, 95%CI 1.28-6.20 in the RPL group.In IVF patients with a history of RPL, subsequent deliveries were associated with a limited number of placental lesions, yet with similar obstetric outcomes.

Does endometriosis have an effect on the placental histopathology pattern and perinatal outcome in singleton live births resulting from IVF treatment?Retrospective cohort study evaluating the data on all live births following IVF treatment between 2009 and 2017 at one university-affiliated tertiary hospital. All patients had placentas sent for full gross and histopathology assessment, irrespective of complication status or delivery mode. The primary outcomes of the study included anatomical, inflammation, vascular malperfusion and villous maturation placental disorders. The secondary outcomes included fetal, maternal, perinatal and delivery complications. A multivariate logistic model was used to adjust the results for confounding factors potentially associated with significant placental characteristics.A total of 1057 live births were included in the final analysis and were allocated to the group of women with endometriosis (n = 75) and those without (n = 982). After adjustment for confounding factors, endometriosis was found to be significantly associated with acute chorioamnionitis with moderate to severe maternal (odds ratio [OR] 2.2, 95% confidence interval [95% CI] 1.1-4.6) and fetal (OR 4.9, 95% CI 1.8-13.1) inflammatory response, placenta previa (OR 3.1, 95% CI 1.2-7.8), subchorionic fibrin deposition (OR 3.4, 95% CI 1.2-9.1), intervillous thrombosis (OR 3.4, 95% CI 1.5-8.1), and fetal vascular malperfusion (OR 5.1, 95% CI 1.4-18.1), as well as with preterm birth (OR 2.5, 95% CI 1.4-4.7).Endometriosis has a significant impact on the placental histopathology and is associated with a higher incidence of preterm birth.

STUDY QUESTION Does embryo vitrification affect placental histopathology pattern and perinatal outcome in singleton live births? SUMMARY ANSWER Embryo vitrification has a significant effect on the placental histopathology pattern and is associated with a higher prevalence of dysfunctional labor. WHAT IS KNOWN ALREADY Obstetrical and perinatal outcomes differ between live births resulting from fresh and frozen embryo transfers. The effect of embryo vitrification on the placental histopathology features associated with the development of perinatal complications remains unclear. STUDY DESIGN, SIZE, DURATION Retrospective cohort study evaluating data of all live births from one academic tertiary hospital resulting from IVF treatment with autologous oocytes during the period from 2009 to 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients had placentas sent for pathological evaluation irrelevant of maternal or fetal complications status. Placental, obstetric and perinatal outcomes of pregnancies resulting from hormone replacement vitrified embryo transfers were compared with those after fresh embryo transfers. A multivariate analysis was conducted to adjust the results for determinants potentially associated with the development of placental histopathology abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE A total of 1014 singleton live births were included in the final analysis and were allocated to the group of pregnancies resulting from fresh (n = 660) and hormone replacement frozen (n = 354) embryo transfers. After the adjustment for confounding factors the frozen embryo transfers were found to be significantly associated with chorioamnionitis with maternal (odds ratio (OR) 2.0; 95% CI 1.2–3.3) and fetal response (OR 2.6; 95% CI 1.2–5.7), fetal vascular malperfusion (OR 3.9; 95% CI 1.4–9.2), furcate cord insertion (OR 2.3 95% CI 1.2–5.3), villitis of unknown etiology (OR 2.1; 95% CI 1.1–4.2), intervillous thrombi (OR 2.1; 95% CI 1.3–3.7), subchorionic thrombi (OR 3.4; 95% CI 1.6–7.0), as well as with failure of labor progress (OR 2.5; 95% CI 1.5–4.2). LIMITATIONS, REASONS FOR CAUTION Since the live births resulted from frozen-thawed embryos included treatment cycles with previously failed embryo transfers, the factors over embryo vitrification may affect implantation and placental histopathology. WIDER IMPLICATIONS OF THE FINDINGS The study results contribute to the understanding of the perinatal future of fresh and vitrified embryos. Our findings may have an implication for the clinical decision to perform fresh or frozen-thawed embryo transfer. STUDY FUNDING/COMPETING INTEREST(s) Authors have not received any funding to support this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

To assess placental histological findings following assisted hatching in fresh transfer in vitro fertilization cycles.Evaluation of a historic cohort of live singleton deliveries after fresh embryo transfer (ET) at a single university medical center between 2009 and 2017. We compared perinatal outcomes and placental histology in cases where assisted hatching was performed prior to ET (AH group) and cases with no AH (no AH group).Overall, 166 deliveries following AH were compared to 494 deliveries with no AH. Patients' demographics were similar between the groups. Median antral follicle count was significantly lower in the AH group, median 11 (range 1-50) vs. 16 (range 1-80), p 0.001, and the primary indication for infertility treatment significantly more often diminished ovarian reserve (p 0.001). Cycle characteristics in the AH group included a higher gonadotropin dose employed, and a lower rate of single and blastocyte transfer. Pregnancies following AH were associated with less low-lying placentas, 0.6% vs. 6.2%, p = 0.001, and comparable for other perinatal outcomes. After adjusting for confounders, the rate of bilobated placentas was higher following AH, aOR 7.10, 95% CI 1.50-33.51. The rate of perivillous depositions was higher with AH, aOR, 95% CI 3.18, 1.46-6.93, and the rate of chorangiosis lower in this group, aOR, 95% CI 0.32, 0.11-0.93. The overall rate of vascular lesions was similar between the groups.Pregnancies following AH are notable for a lower rate of placenta previa, yet a higher rate of bilobated placentas and perivillous depositions and less chorangiosis, warranting further investigation.

Granulosa cells of growing ovarian follicles elaborate filopodia-like structures termed transzonal projections (TZPs) that supply the enclosed oocyte with factors essential for its development. Little is known, however, of the mechanisms underlying the generation of TZPs. We show in mouse and human that filopodia, defined by an actin backbone, emerge from granulosa cells in early stage primary follicles and that actin-rich TZPs become detectable as soon as a space corresponding to the zona pellucida appears. mRNA encoding Myosin10 (MYO10), a motor protein that accumulates at the base and tips of filopodia and has been implicated in their initiation and elongation, is present in granulosa cells and oocytes of growing follicles. MYO10 protein accumulates in foci located mainly between the oocyte and innermost layer of granulosa cells, where it colocalizes with actin. In both mouse and human, the number of MYO10 foci increases as oocytes grow, corresponding to the increase in the number of actin-TZPs. RNAi-mediated depletion of MYO10 in cultured mouse granulosa cell-oocyte complexes is associated with a 52% reduction in the number of MYO10 foci and a 28% reduction in the number of actin-TZPs. Moreover, incubation of cumulus-oocyte complexes in the presence of epidermal growth factor, which triggers a 93% reduction in the number of actin-TZPs, is associated with a 55% reduction in the number of MYO10 foci. These results suggest that granulosa cells possess an ability to elaborate filopodia, which when directed toward the oocyte become actin-TZPs, and that MYO10 increases the efficiency of formation or maintenance of actin-TZPs.