The effect of oestrogen dose and duration in programmed frozen cycles on obstetric outcomes and placental findings.

RESEARCH QUESTION: Does programmed frozen embryo transfer (FET) with high-dose oestrogen affect obstetric outcomes and placental findings? DESIGN: A retrospective cohort of live singleton deliveries at a single institution between 2009 and 2017, including deliveries attained by IVF with programmed FET; oocyte recipients were excluded. High-dose oestrogen was defined as a daily dose >6 mg throughout treatment. All placentas were evaluated regardless of complication status and the Amsterdam classification was used to analyse findings. RESULTS: A total of 57 deliveries in the high-dose oestrogen group were compared with 274 controls. The high-dose oestrogen group displayed significantly longer duration of oestrogen treatment (18.8 ± 4.9 versus 13.3 ± 2.7 days, P < 0.001), total cumulative oestrogen dose (149.7 ± 46.1 versus 80.3 ± 16.8 mg, P < 0.001) and lower endometrial thickness (8.5 ± 1.4 versus 9.8 ± 1.7 mm, P < 0.001). After adjustment for confounders, higher dose oestrogen was found to be associated with a lower average birthweight (coefficient -252.4 g, 95% confidence interval [CI] -483.5 to -21.2), a higher rate of low-birthweight neonates (adjusted odds ratio [aOR] 4.88, 95% CI 1.05 to 22.57), bilobated placentas (aOR 3.36, 95% CI 1.04 to 10.89), accessory lobes (aOR 8.74, 95% CI 1.24 to 61.5), accelerated villous maturation (aOR 2.06, 95% CI 1.09 to 3.87), retroplacental haematoma (aOR 5.39, 95% CI 1.11 to 26.13) and maternal malperfusion lesions (aOR 1.46, 95% CI 1.04 to 2.05). CONCLUSION: A higher daily oestrogen dose in programmed FET is associated with low birthweight and placental changes, although this may relate to altered endometrial properties and not to the treatment itself.

Does a history of recurrent pregnancy loss affect subsequent obstetric outcomes and placental findings in in vitro fertilization?

PURPOSE: To assess perinatal outcomes and placental findings in in vitro fertilization (IVF) patients with previous recurrent pregnancy loss (RPL). METHODS: 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. RESULTS: 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, ß - 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. CONCLUSION: In IVF patients with a history of RPL, subsequent deliveries were associated with a limited number of placental lesions, yet with similar obstetric outcomes.

Placental histology and pregnancy complications following intracytoplasmic sperm injection for non-male factor infertility.

PURPOSE: To assess obstetric outcomes and placental histology following intracytoplasmic sperm injection (ICSI), for non-male infertility. METHODS: This was a retrospective cohort of live born singleton deliveries after in vitro fertilization (IVF) at a single university affiliated medical center between 2009 and 2017. Excluded were IVF cycles with male infertility and oocyte recipients. We compared obstetric outcomes and placental histology in cases ICSI was performed (ICSI group) and cases with no ICSI (IVF group). RESULTS: A total of 400 deliveries following ICSI were compared to 218 in the IVF group. Maternal age was similar between the groups, while diminished ovarian reserve was more common among ICSI patients and tubal disease less common (p < 0.001). The rate of blastocyte transfer was also significantly lower in the ICSI group-67.5% vs. 77%, p = 0.01. Pregnancies following ICSI were characterized by similar rates of preeclampsia, preterm birth, and small for gestational age neonates. Although cesarean delivery rate was significantly higher in the group, this did no attain significance after adjustment for confounders. Placentas in the ICSI group were notable for a lower rate of villitis of unknown etiology (1% vs. 4.5%, p = 0.007) and a higher rate of maternal surface calcifications (33% vs. 23.8%, p = 0.01) after adjustment for confounders. CONCLUSION: The employment of ICSI with no male indication is associated with similar obstetric outcomes. Despite isolated placental differences among many investigated, placental histology seems overall comparable as well. These results are reassuring to clinicians and patients.

Effect of newborn gender on placental histopathology and perinatal outcome in singleton live births following IVF.

RESEARCH QUESTION: Does newborn gender affect placental histopathology pattern and perinatal outcome in singleton live births following IVF treatment? DESIGN: Retrospective cohort study evaluating data of all live births from one academic tertiary hospital following IVF treatment during 2009-2017. All patients had placentas sent for pathological evaluation irrelevant of maternal and fetal complications status. Exclusion criteria were abnormal uterine cavity findings, previous uterine surgery, in-vitro maturation cycles, gestational carrier cycles, oocyte recipient cycles, preimplantation genetic diagnosis cycles and multiple pregnancies. The primary outcomes included anatomical, inflammation, vascular malperfusion and villous maturation placental features. The secondary outcomes included fetal, maternal, perinatal and delivery complications. A multivariate analysis was conducted to adjust the results for factors potentially associated with placental pathology features. RESULTS: A total of 1057 live births were included in the final analysis and were allocated to the study groups according to fetal gender: males (n = 527) and females (n = 530). After adjustment for potential confounding factors, male gender was significantly associated with villous agglutination (odds ratio [OR] 9.8; 95% confidence interval [CI] 1.4-78.2), avascular villi (OR 4.1; 95% CI 1.3-12.6) and maternal vascular malperfusion (OR 1.8; 95% CI 1.2-2.7). Female gender was significantly associated with bilobed placenta (OR 0.2; 95% CI 0.06-0.8) and subchorionic thrombi (OR 0.5; 95% CI 0.3-0.9). The prevalence of adverse fetal, maternal and delivery outcomes was similar between the groups. CONCLUSIONS: Newborn gender has a significant impact on the placental histopathology pattern, which can contribute to the development of adverse perinatal outcomes.

Impact of intramural non-cavity-distorting leiomyoma on placental histopathology and perinatal outcome in singleton live births resulting from in vitro fertilization treatment.

PURPOSE: To evaluate the effect of non-cavity-distorting intramural leiomyomas on the placental histopathology pattern and perinatal outcome in singleton live births resulting from in vitro fertilization treatment. METHODS: The study population included all singleton live births following in vitro fertilization treatment with autologous oocytes during the period from 2009 to 2017. Primary outcomes included anatomical, inflammation, vascular malperfusion, and villous maturation placental features. Secondary outcomes included fetal, maternal, delivery, and perinatal complications. RESULTS: A total of 1119 live births were included in the final analysis and were allocated to the group of pregnancies with non-cavity-distorting intramural myomas (n = 101) and without myomas (n = 1018). After the adjustment for confounding factors, the non-cavity-distorting intramural myomas were found to be significantly associated with assisted placental delivery (OR 2.4; 95% CI 1.5-3.9), furcate cord insertion (OR 3.6; 95% CI 1.4-9.3), circumvallate membranes insertion (OR 5.2; 95% CI 1.4-19.3), chronic deciduitis (OR 8.2; 95% CI 1.6-42.2), focal intramural fibrin deposition (OR 25.1; 95% CI 2.1-306.2), subchorionic thrombi (OR 3.6; 95% CI 1.7-7.6), maternal vasculopathy (OR 2.5; 95% CI 1.2-5.5), and chorangioma (OR 5.9; 95% CI 1.4-25.2) as well as with the failure of labor progress (OR 2.4; 95% CI 1.3-4.4) and induction (OR 3.2; 95% CI 1.2-9.0). CONCLUSION: Intramural non-cavity-distorting myomas have a significant impact on the placental histopathology with a higher incidence of dysfunctional labor.

The Placenta in Neonatal Encephalopathy: A Case-Control Study.

OBJECTIVE: We assessed whether specific histologic placental lesions were associated with risk for neonatal encephalopathy, a strong predictor of death or cerebral palsy. STUDY DESIGN: Case-control study of singletons with gestational ages ≥35 weeks. Data were abstracted from a prospectively collected database of consecutive births at a hospital in which placental samples from specified sites are collected and stored for all inborn infants. Placentas of infants with neonatal encephalopathy were compared with randomly selected control infants (ratio of 1:3). Placental histologic slides were read by a single experienced perinatal pathologist unaware of case status, using internationally recommended definitions and terminology. Findings were grouped into inflammatory, maternal, or fetal vascular malperfusion (FVM) and other lesions. RESULTS: Placental samples were available for 73 of 87 (84%) cases and 253 of 261 (97%) controls. Delivery complications and gross placental abnormalities were more common in cases, of whom 4 died. Inflammation and maternal vascular malperfusion did not differ, and findings consistent with global FVM were more frequent in case (20%) than control (7%) placentas (P = .001). There was a trend toward more segmental FVM and high-grade FVM (fetal thrombotic vasculopathy) among cases. Some type of FVM was observed in 24% of placentas with neonatal encephalopathy. In infants with both neonatal encephalopathy and placental FVM, more often than in infants with neonatal encephalopathy without FVM, electronic fetal monitoring tracings were considered possibly or definitely abnormal (P = .028). CONCLUSIONS: Vascular malperfusion of subacute or chronic origin on the fetal side of the placenta was associated with increased risk of neonatal encephalopathy.

Effect of Parity on Placental Histopathology Features in Singleton Live Births Following IVF.

The aim of this study was to evaluate the effect of parity (primipara vs multipara) on the histopathology of the placenta in singleton live births following in vitro fertilization. We conducted a retrospective cohort study evaluating data of all IVF resulted live births from one university affiliated hospital during 2009-2017. All patients had the placenta sent for pathological evaluation. Exclusion criteria were history of miscarriage or elective termination of pregnancy, abnormal uterine cavity findings, previous uterine surgery, in vitro maturation cycles, gestational carrier cycles, oocyte recipient cycles, preimplantation genetic diagnosis cycles, and multiple pregnancies. The outcomes measured included anatomical, inflammation, vascular malperfusion, and villous maturation placental features. A multivariate analysis was conducted to adjust the results for factors potentially associated with placental pathology features. A total of 395 live births were included in the final analysis and were allocated to the study groups according to parity: primipara (n = 273) and multipara (n = 122). After adjustment for potential confounding factors, multiparity was found to be significantly associated with delayed villous maturation (OR 4.9; 95% CI 1.2-19.8) and primiparity was significantly associated with maternal vascular malperfusion (OR 0.6; 95% CI 0.3-0.8). We showed that parity has an impact on placental histopathological changes which in turn may affect perinatal outcome.

The impact of polycystic ovary syndrome on placental histopathology patterns in in-vitro fertilization singleton live births.

INTRODUCTION: Pregnant polycystic ovary syndrome (PCOS) patients are at increased risk for myriad obstetric complications, with the placenta thought to play a key role in their development. We aimed to evaluate placental histopathology patterns in placentas of women with PCOS who underwent in-vitro-fertilization (IVF). METHODS: This retrospective study utilized full gross and histopathologic assessment of placentas of all women who had IVF treatment and delivered at the Royal Victoria Hospital from 2009 to 2017, regardless of complications or mode of delivery. Pathologic findings included anatomic, inflammation, villous maturation, and vascular mal-perfusion features. Placentas of PCOS women were compared to those of ovulatory controls. Multivariate logistic regression was used to adjust results for confounding factors potentially associated with significant placental and perinatal characteristics. RESULTS: Women with PCOS (n = 47) were more likely to develop gestational diabetes mellitus compared to ovulatory controls (n = 1121) (38.3% vs. 9.8%, p < 0.001). Placentas from PCOS women were more likely circumvallate placentas (aOR 8.3, 95%CI 1.9-37.3) and more likely to have a hypercoiled umbilical cord (aOR 6.8 95%CI 1.3-36.8) and villitis of unknown etiology (aOR 6.1, 95%CI 1.5-25.6). There was an increased likelihood of chorangiosis (aOR 2.7, 95% CI 1.3-5.8), evidence of fetal vascular malperfusion based on one criteria (aOR 2.7, 95%CI 1.1-7.4), or more than one criteria (aOR 6.4, 95%CI 1.6-25.9), more nucleated fetal red blood cells (aOR 5.2, 95%CI 1.1-24.5), and a higher likelihood of chorangiomas (aOR 9.4, 95%CI 1.6-55.1) in placentas from PCOS women than in controls. DISCUSSION: IVF pregnancies' placental histopathological characteristics are significantly impacted by an underlying diagnosis of PCOS, including important anatomic changes and vascular placental abnormalities.