Similar Pregnancy Outcomes Research Articles

High androgen level during controlled ovarian stimulation cycle impairs endometrial receptivity in PCOS patients

PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity.

Vaginal Progesterone Gel versus Intramuscular Progesterone for Luteal Phase Support in Suboptimal Responders Undergoing Assisted Reproductive Cycles

Background: The purpose of this research is to compare the efficacy of 8% micronized vaginal progesterone gel (VAG) at 180 mg daily versus intramuscular progesterone (IMP) in oil at 100 mg daily for luteal phase support (LPS) after fresh single embryo transfer (SET) in Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Group 1b patients, and to ascertain whether the type of LPS predicts live birth in these patients. Methods: A total of 2420 assisted reproductive technology (ART) cycles performed in Ondokuz Mayıs University IVF Unit were analysed retrospectively. The data of POSEIDON Group 1b (unexpected suboptimal responders) who underwent antagonist in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were included. All patients were categorized into groups according to the form of LPS, specifically VAG and IMP. Pregnancy, clinical pregnancy rate (CPR), live birth rate (LBR), spontaneous abortion rate and predictors of live birth (age, infertility duration, body mass index (BMI), type of progesterone used for luteal support, serum day 3 estradiol, serum progesterone on the day of human coryonic gonadotrophin (HCG), total duration of induction, serum estradiol on the day of HCG, the total number of oocytes retrieved, number of mature oocytes obtained, average gonadotropin dose per day, total gonadotropin dose administered and total number of embryos retrieved) were analyzed. Results: There was no statistically significant difference between the micronized VAG and IMP groups in terms of age (31 (23–35) vs. 27 (23–35), p = 0.319). There were no statistically significant differences in pregnancy outcomes between the two groups concerning CPR per transfer (70.6% vs. 75.6%; p = 0.364), ongoing pregnancy per cycle (36.2% vs. 39.5%; p = 0.577), and LBR per cycle (34.4% vs. 36.1%; p = 0.785). The spontaneous abortion rates (36.2% vs. 36.8%; p = 0.921) were similar between VAG and IMP groups. The type of LPS did not emerge as a parameter predicting pregnancy (odds ratio (OR): 0.718, 95% confidence interval (95% CI): 0.652–1.313, p = 0.451), clinical pregnancy (OR: 0.598, 95% CI: 0.592–1.289, p = 0.562) and live birth (OR: 0.802, 95% CI: 0.661–1.202, p = 0.580). The logistic regression analysis aimed at assessing the influence of confounding factors, namely age, BMI, and duration of infertility on pregnancy rate, CPR and LBR, did not reveal statistically significant results (p > 0.05). Conclusions: VAG 180 mg daily provide similar pregnancy outcomes compared to 100 mg daily IMP in POSEIDON Group 1b patients undergoing antagonist fresh IVF/ICSI cycles.

Day 2 versus day 3 embryo transfer in patients with in vitro fertilization and only one zygote with two pronuclei.

This study aimed to compare the pregnancy outcomes of Day 2 (D2) fresh embryo transfer and D3 fresh embryo transfer in women with only one zygote with two pronuclei (2PN). Data on 432 in vitro fertilization-embryo transfer cycles with only one 2PN zygote from January 2016 to January 2022 were retrospectively collected. A total of 302 fresh embryo transfers on D2 (n = 193) and D3 (n = 109) were analyzed, and pregnancy outcomes were compared. The patients' characteristics were not different between D2 and D3 embryo transfer. There were no significant differences in the rates of clinical pregnancy, early abortion, or live birth between D2 and D3 embryo transfer. A multivariate logistic regression model controlling for age, the fertilization method, the number of oocytes harvested, and the number of high-quality embryos transferred showed that the live birth rate was similar between D2 and D3 embryo transfer. In in vitro fertilization-embryo transfer cycles with only one 2PN zygote, D2 fresh embryo transfer may provide similar pregnancy outcomes to those of D3 embryo transfer. D2 embryo transfer may be an option because of the risk of cycle cancellation due to the absence of viable embryos on D3.

Pregnancy outcomes in infertile patients with endometrial hyperplasia with or without atypia undergoing in vitro fertilization: the early-follicular long protocol is superior to midluteal long protocol.

Although in vitro fertilization (IVF) in infertile patients with endometrial hyperplasia is common after drug treatment, the pregnancy outcomes are often unsatisfactory. Till date, no studies have reported the outcome of patients with endometrial hyperplasia treated using early-follicular long (EL) protocol and midluteal long (ML) protocol. To evaluate the pregnancy outcomes and disease prognosis of patients with endometrial hyperplasia with or without atypia undergoing IVF treatment with EL protocol or ML protocol. This was a retrospective study in university-affiliated reproductive medical center. A total of 138 patients with endometrial hyperplasia undergoing IVF treatment were included to compare the pregnancy outcomes and disease prognosis between EL and ML protocols. We further matched 276 patients with normal endometrium to compare the pregnancy outcomes between patients with endometrial hyperplasia and patients with normal endometrium under different controlled ovarian stimulation (COS) protocol. In patients with endometrial hyperplasia, the clinical pregnancy rate (CPR) and live birth rate (LBR) were significantly higher in EL protocol than in ML protocol (61.8% vs. 43.5%, P=0.032; 50.0% vs. 30.6%, P= 0.022). In the ML protocol, patients with endometrial hyperplasia had significantly lower CPR and LBR than those with normal endometrium (43.5% vs. 59.7%, P=0.037; 30.6% vs. 49.2%, P=0.016). While in the EL protocol, they achieved similar CPR and LBR as patients with normal endometrium (61.8% vs. 69.7%, P=0.232; 50.0% vs. 59.9%, P=0.156). In patients with endometrial hyperplasia, COS protocol was an independent factor affecting clinical pregnancy (adjusted odds ratio [OR] 2.479; 95% confidence interval [CI] 1.154-5.327) and live birth (adjusted OR 2.730; 95% CI 1.249-5.966). After 1-10 years of follow-up, no significant difference was found in the recurrence rate of endometrial lesions between both treatment groups. For patients with endometrial hyperplasia undergoing IVF treatment, the EL protocol is superior to ML protocol, and in the EL protocol, they can achieve similar pregnancy outcomes as patients with normal endometrium.

A comparative analysis of the clinical pregnancy and perinatal outcomes between oocyte vitrification and embryo vitrification based on the propensity score matching method.

This study investigated the safety and effectiveness of oocyte vitrification by comparing the clinical pregnancy and perinatal outcomes between transfer cycles of vitrified oocytes and those of vitrified embryos. A retrospective cohort study was conducted to analyze the clinical data of patients who underwent cleavage-stage embryo transfer at the Department of Reproductive Medicine between January 2011 and June 2021. Seventy-seven transfer cycles of fresh cleavage-stage embryos developed from vitrified-thawed oocytes (oocyte vitrification group) and 2170 transfer cycles of vitrified-thawed cleavage-stage embryos developed from fresh oocytes (embryo vitrification group) were included. Further, 293 cases were selected from the embryo vitrification group after applying propensity score matching at 1:4. The primary outcomes were miscarriage rate, live birth rate, and neonatal birth weight. No statistically significant differences were observed in the baseline data, pregnancy, perinatal outcomes, or neonatal outcomes for either singleton or twin births between the two groups after matching. Backwards stepwise regression was used to analyze the length of gestation. The age of female participants (β = - 0.410, 95% CI = - 1.339 ~ - 0.620, P < 0.001) had a statistically significant effect. Oocyte vitrification results in similar clinical pregnancy and perinatal outcomes as does embryo vitrification; hence, it is a relatively safe assisted reproductive technique.

Progestins for pituitary suppression during ovarian stimulation in artificial reproductive technology

Background: Progestins can suppress endogenous luteinizing hormone secretion from the pituitary gland. Progestins can be used orally and are less expensive than gonadotrophin-releasing hormone (GnRH) analogs. However, early endometrial exposure to progestin precludes fresh embryo transfer (ET), but the emergence of vitrification for oocyte cryopreservation cycles allows more opportunities for using progestins for pituitary suppression.&#x0D; Objective: To assess the mechanism of pituitary suppression by progestins, the effectiveness of progestins compared with GnRH analogs, the effect of progestins on oocyte and embryo developmental potential and euploidy status, and the cost-effectiveness of progestin-primed stimulation. &#x0D; Methods: A literature search using the keywords “multiple waves of antral ovarian follicular development, In Vitro Fertilization, Ovarian stimulation ” was performed in the PubMed database.&#x0D; Results: The duration of stimulation, gonadotrophin consumption, and oocyte yield were similar in progestins and GnRH analogs. However, progestins were associated with significantly lower gonadotrophin consumption than their analogs. Overall, live birth and clinical pregnancy rates per ET were similar to those of progestins and GnRH analogs. Studies comparing medroxyprogesterone acetate, dydrogesterone, and micronized progesterone suggest similar ovarian responses and pregnancy outcomes. The euploidy status of embryos and obstetric and neonatal outcomes from progestin-primed cycles are similar to those of embryos from conventional stimulation cycles. Despite the lower cost of progestins than GnRH analogs, the mandatory cryopreservation of all embryos followed by a deferred transfer may increase the cost per live birth with progestins compared with an artificial reproductive technology cycle culminating in a fresh ET.&#x0D; Conclusion: Progestins present an effective option for women who do not contemplate a fresh ET, e.g., fertility preservation, anticipated hyper responders, preimplantation genetic testing, oocyte donors, and double stimulation cycles.

Similar pregnancy outcomes from fresh and frozen donor oocytes transferred to gestational carriers: a SART database analysis isolating the effects of oocyte vitrification.

This work aimed to study clinical and neonatal outcomes of embryos derived from frozen compared to fresh donor oocytes in gestational carrier cycles. This is a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database between 2014 and 2015, comprising of 1284 fresh transfer cycles to gestational carrier recipients of embryos resulting from fresh (n = 1119) and vitrified/thawed (n = 165) donor oocytes. Models were adjusted for gestational carrier age, preimplantation genetic testing (PGT-A), number of embryos transferred, multiple gestation, and fetal heart reduction. As our models were part of a larger analysis, intended parent BMI, smoking status, and parity were also adjusted for, but did not influence outcomes in this analysis. There was no significant difference in probability of live birth rates when comparing embryos derived from fresh and frozen donor oocytes in gestational carrier cycles. There were also no significant differences in biochemical pregnancy losses or clinical miscarriage. There were no significant differences noted in low birthweight or high birthweight infants derived from fresh versus frozen donor oocyte after transfer into a gestational carrier. The analysis of fresh and frozen donor oocytes in gestational carrier cycles provides the opportunity to assess for a possible effect of vitrification on the oocyte by controlling for differences in the uterine environment. We observed no significant differences in live birth, pregnancy loss, low birthweight or high birthweight infants when comparing fresh and frozen donor oocytes in gestational carrier cycles.

Fondaparinux Results in Similar Pregnancy Outcomes with Lower Adverse Reaction Rates Compared to Low Molecular Weight Heparin in Chinese Recurrent Miscarriage Women.

Fondaparinux inhibits thrombin generation by inactivating factor Xa, which has the potential to treat recurrent miscarriage (RM). However, more clinical evidence is required to support its application in Chinese women with RM. This research aimed to compare the live birth rate, gestational weeks at delivery, birth weight, Apgar score of newborns, and adverse reaction rates between fondaparinux and low molecular weight heparin (LMWH) in Chinese women with RM. Totally, 132 women with RM treated with fondaparinux or LMWH were included in this retrospective study. According to the corresponding treatment, women with RM were divided into the fondaparinux cohort (N = 45) and LMWH cohort (N = 87). The live birth rate was 68.9% in the fondaparinux cohort and 56.3% in the LMWH cohort, which was not different between the two cohorts (P = 0.161). Multivariable logistics regression analysis suggested that only previous miscarriage times (≥ 4 times vs. < 4 times) were independently related to a lower possibility of live birth in women with RM (odds ratio = 0.431, P = 0.036). It was also observed that gestational weeks at delivery (38.1 ± 1.4 vs. 37.7 ± 1.7 weeks) (P = 0.258), birth weight (2,923.7 ± 355.0 vs. 2,807.8 ± 334.0 g) (P = 0.144), and Apgar score of newborns (9.8 ± 0.5 vs. 9.6 ± 0.8) (P = 0.175) were not different between the fondaparinux cohort and LMWH cohort. Inspiringly, the total adverse reaction rate was reduced in the fondaparinux cohort vs. the LMWH cohort (20.0% vs. 37.9%) (P = 0.036). Fondaparinux results in similar pregnancy outcomes with lower adverse reaction rates compared to LMWH in Chinese women with RM.

Characterizing Pregnancy Outcomes in a Humanized Mouse Model of Sickle Cell Disease

Background: Sickle cell disease (SCD) is a group of hereditary disorders commonly associated with the distortion of red blood cells (RBC) at low oxygen levels. It is characterized by complications such as vaso-occlusion, anemia, and hemolysis. These complications are lifelong and become extremely relevant during periods of increased physiological stress such as pregnancy. Pregnancy in sickle cell disease (SCD) is associated with an increased risk of complications including, pre-term delivery, deep vein thrombosis, intra-uterine growth restriction, pre-eclampsia, and intra-uterine death. Recent meta-analyses have shown that women with SCD are at 26x greater risk for maternal mortality than their healthy counterparts; a figure which, despite the adoption of improved care plans, has shown little to no significant improvement over the last two decades. While impaired vascular maintenance underlies multiple complications of pregnancy outside of sickle cell disease, it is especially relevant to, and characteristic of sickle cell-related pathologies at baseline and is highly likely to be exacerbated as pregnancy proceeds. Through this study we aimed to characterize the effects of SCD-related vasculopathy on pregnancy outcomes and overall placental health using the Townes humanized mouse model of SCD. Methods: SS (sickle hemoglobin) and AA (normal hemoglobin) mice underwent timed breeding to produce pregnant dams. These dams were housed under normal conditions until 17.5 days post conception (dpc), at which point they began undergoing procedures for analysis including 24-hour urine collection, high-resolution ultrasound analysis (18.5dpc), and post-mortem analysis of pregnancy outcomes and tissue collection (18.5dpc). Included in this report are gross pregnancy outcomes, histological assessments of placental tissue, and reports from ultrasound analysis including 3-D volume measures, placental vascularization renders, and laser-Doppler assessment of uterine and umbilical arteries. Continuing research efforts will further utilize tissues from this study to evaluate the biochemical interactions influencing poor pregnancy outcomes related to SCD. Results: These studies show that the SCD mice recapitulate many similarly poor outcomes as women. We observed: reduced litter sizes (AA 6.9 ± 1.5 embryos vs SS 5.2 ± 1.2 embryos**), fetal weight (AA 0.49 ± 0.14g vs SS 0.38 ± 0.16g*), viability of embryos (AA 100.0% IQR 0.0 vs SS 20.0% IQR 33.3****), and maternal mortality (AA 0.0% vs SS 8.7%, OR = 4.3 ns). In assessing placental histology, we identified evidence of vasculopathy common to end organ damage in SCD such as increased presence of avascular areas, reduced relative labyrinth area (AA 55.6 ± 8.6% vs SS 44.7 ± 6.0%*) and reduced vascular density (AA 38.9 ± 6.2% vs SS 34.4 ± 7.0%*) which are likely responsible for worsening outcomes. Additional pathologies include increased occurrence of placental ectasia, calcification of the labyrinth, vascular thrombi, and perivascular fibrosis when compared to controls. Further, ultrasound analysis revealed several measures of placental insufficiency amongst SS mice that were significantly impaired including uterine blood flow and an overall reduction in placental vascularization and oxygenation. Conclusions: SCD mice demonstrate many similar pregnancy outcomes as humans, allowing for increased translational application. We've shown these outcomes to be severe and largely driven by vascular impairment specifically within the placenta, the main maternal-fetal interface. This study serves as the groundwork for future studies aimed at investigating the underlying mechanisms of these outcomes while also establishing baseline measures and novel methods of approach towards the broader goal of improving obstetric disparities faced by women with SCD.

D6 high-quality expanded blastocysts and D5 expanded blastocysts have similar pregnancy and perinatal outcomes following single frozen blastocyst transfer.

We compared the pregnancy and perinatal outcomes between expanded blastocysts vitrified on D5 versus D6 following single frozen blastocyst transfer. Clinical data on 7,606 cycles of frozen-thawed blastocyst implantations were retrospectively analyzed. Depending on whether blastocysts were vitrified on D5 or D6 and the transferred blastocysts, the blastocysts were divided into 6 groups: HQB-D5, HQB-D6, 4XC-D5, 4XC-D6, 4CX-D5, and 4CX-D6 groups. The differences in clinical pregnancy rate, live birth rate, first trimester abortion rate, preterm birth rate, gestational age, birth weight, and sex ratio at birth among the groups were compared. Our study showed that there was no difference in pregnancy and perinatal outcomes between the delayed formation of D6 high-quality expanded blastocysts and D5 expanded blastocysts, whether they were high-quality blastocysts or not. For low-quality blastocysts, the clinical pregnancy rate of D5 was higher than that of D6, and D5 was also better than D6 in live birth rate for those with inner cell mass rating B or above, while there was no difference between D5 and D6 for those with inner cell mass rating C. Based on our research, we suggest that when we are developing the implantation strategy, we give priority to the selection of high-quality expanded blastocysts, regardless of D5 and D6, whose clinical outcomes are not different. For low-quality blastocysts, D5 expanded blastocysts are preferred for transfer.

Comparison of Breastfeeding Practices in Mothers With Chronic Kidney Disease With or Without Kidney Transplantation.

Introduction: Existing literature on pregnant patients with chronic kidney disease (CKD) with or without kidney transplantation focuses mainly on their pregnancy outcomes, but there are scant data on their lactation outcomes. Our objective was to characterize the lactation outcomes of patients with CKD with or without kidney transplantation. Methods: This is a single-institution retrospective cohort study of female-identifying patients with CKD with or without kidney transplantation who had a birth hospitalization at a tertiary health system between 2010 and 2020. Maternal and pediatric data on medical history, pregnancy, delivery, neonatal, and lactation outcomes, medications, and care team involved were collected. Primary outcome measures were breastfeeding initiation within 24-hour postpartum, breastfeeding 8 or more times per day during hospitalization, and any breastfeeding beyond 1 month. Health professionals' comments related to lactation and medications were extracted for qualitative data analysis. Results: Patients with and without kidney transplantation had similar comorbidities, pregnancy, delivery, and neonatal outcomes, and hospital length of stay (p > 0.05). Patients without kidney transplantation were more likely to initiate breastfeeding in the first 24 hours (p = 0.03) after delivery and continue breastfeeding beyond 1 month postpartum. There was a lack of consistency between specialties regarding medication compatibility with lactation. Patients on immunosuppression were more likely to exclusively formula feed (p = 0.02) or to initiate breastfeeding and then switch to formula (p = 0.0004) because of their immunosuppressive medications versus patients on any other medication. Conclusion: Patients with CKD but without a kidney transplantation were more likely to initiate breastfeeding or provide breast milk to their infant within 24 hours of delivery, breastfeed >8 times per day during their hospital stay, and breastfeed beyond a month postpartum than those with a transplanted kidney. Lactation support and pharmacology should be incorporated into graduate medical education.

Impact of experiencing multiple vulnerabilities on fetal growth and complications in women with hyperglycemia in pregnancy

BackgroundIn women with hyperglycemia in pregnancy living in France, psychosocial deprivation is associated with both earlier and greater exposure to the condition, as well as poorer maternofetal prognosis. We explored the impact of this and two other socioeconomic vulnerability indicators—food insecurity and poor language proficiency—on adherence to prenatal care and maternal and fetal outcomes.MethodsIn a socially deprived suburb of Paris, we selected women who delivered between 01/01/2012 and 31/12/2018 and received care (nurse, dietician, diabetologist evaluation, advice, regular follow-up to adjust insulin doses if requested) for hyperglycemia in pregnancy. We analyzed the associations between individual psychosocial deprivation, food insecurity, French language proficiency (variables assessed by individual questionnaires) and fetal growth (main outcome), as well as other core maternal and fetal outcomes.ResultsAmong the 1,168 women included (multiethnic cohort, 19.3% of whom were Europeans), 56%, 17.9%, and 27.5% had psychosocial deprivation, food insecurity, and poor French language proficiency, respectively. Forty-three percent were prescribed insulin therapy. Women with more than one vulnerability had more consultations for diabetes. The rates for small (SGA), appropriate (AGA), and large-for-gestational-age (LGA) infant were 11.4%, 76.5% and 12.2%, respectively. These rates were similar in women with and without psychosocial deprivation, and in those with and without food insecurity. Interestingly, women with poor French language proficiency had a higher odds ratio of delivering a small- or large-for-gestational age infant than those with good proficiency.ConclusionWe found similar pregnancy outcomes for women with hyperglycemia in pregnancy living in France, irrespective of whether or not they had psychosocial deprivation or food insecurity. Optimized single-center care with specialized follow-up could contribute to reduce inequalities in maternal and fetal outcomes in women with hyperglycemia in pregnancy.

Pregnancy outcomes following natural conception and assisted reproduction treatment in women who received COVID-19 vaccination prior to conception: a population-based cohort study in China.

The coronavirus disease-2019 (COVID-19) pandemic has swept across the world and continues to exert serious adverse effects on vulnerable populations, including pregnant women and neonates. The vaccines available at present were designed to prevent infection from COVID-19 strains and control viral spread. Although the incidence of pregnancy cycle outcomes are not likely to increase patients vaccinated prior to pregnancy compared with unvaccinated patients based on our knowledge of vaccination safety, there is no specific evidence to support this hypothesis. Therefore, the current study aimed to investigate the association between maternal vaccination prior to conception and pregnancy outcomes. We retrospectively analyzed 2,614 women who received prenatal care and delivered in the Obstetrical Department of The First Affiliated Hospital of Anhui Medical University between February 2022 and November 2022. Of the 1,380 eligible pregnant women, 899 women who had received preconception vaccination were assigned to a vaccine group and 481 women who were not vaccinated were control group. Of the enrolled patients, 291 women received fertility treatment (141 vaccinated women, 150 unvaccinated women). The primary outcomes were pregnancy complications (hypothyroidism, gestational diabetes mellitus, pregnancy-induced hypertension, polyhydramnios, oligohydramnios, premature rupture of membranes and postpartum hemorrhage), obstetric outcomes (preterm birth rate, cesarean section rate) and neonatal outcomes (birth-weight, body length, low-birth-weight rate, rate of congenital defects, neonatal mortality and admission to the neonatal intensive care unit). There was no significant difference in the incidence of complications during pregnancy and delivery when compared between the vaccine group and control group in either univariate- or multivariate-models. The type of vaccine was not associated with the odds of adverse pregnancy outcome. Among the women with infertility treatment, the vaccinated group and the unvaccinated group had similar pregnancy outcomes. Women who received COVID-19 vaccination prior to conception had similar maternal and neonatal outcomes as women who were unvaccinated. Our findings indicate that COVID-19 vaccinations can be safely administered prior to pregnancy in women who are planning pregnancy or assisted reproductive treatment. During new waves of COVID-19 infection, women who are planning pregnancy should be vaccinated as soon as possible to avoid subsequent infections.

Retrospective analysis of the endometrial preparation protocols for frozen-thawed embryo transfer cycles in women with endometriosis

BackgroundThere was inconsistency in optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) in patients with endometriosis. We conducted this study to investigate the effect of different endometrial preparation protocols on the pregnancy outcomes in patients with endometriosis undergoing FET cycles, and determine the optimal number of GnRHa injections in GnRHa-HRT protocols.Method(s)This was a retrospective cohort analysis of women with endometriosis who underwent FET cycles at a single university-based center. This study retrospectively analyzed 2048 FET cycles in our center from 2011 to 2020. According to the endometrial preparation protocols, patients were divided into 4 groups: gonadotropin releasing hormone agonist-hormone replacement therapy(GnRHa-HRT), hormone replacement therapy(HRT), ovulation induction(OI), and natural cycle(NC). In the GnRHa-HRT group, patients were further divided into 3 groups: one injection of GnRHa, two injections of GnRHa, and three or more injections of GnRHa. The primary outcome was the clinical pregnancy rate. Propensity score matching was used to adjust for potential non-similarities among the groups. Multivariate logistic regression analysis was performed to figure out the risk factors for pregnancy outcomes.Result(s)There were no statistical differences in pregnancy outcomes among the four endometrial preparation protocols in FET cycles with endometriosis patients, the results retained after propensity score matching(PSM). And in endometriosis patients complicated with adenomyosis, the results remained similar. In patients with GnRHa-HRT protocol, there were no differences in clinical pregnancy rate and live birth rate with different numbers of GnRHa injections, the early miscarriage rate were 18% in the two injections of GnRHa group and 6.5% in the one injection of GnRHa group(P = 0.017). Multifactorial logistic regression analysis showed that two injections of GnRHa before FET was associated with increased early miscarriage rate compared with one injection of GnRHa[adjusted OR (95% CI): 3.116(1.079–8.998),p = 0.036].Conclusion(s)The four kinds of endometrial preparation protocols for FET, GnRHa-HRT, HRT, OI and NC had similar pregnancy outcomes in patients with endometriosis. In endometriosis patients complicated with adenomyosis, the results remained similar. In patients with endometriosis undergoing GnRHa-HRT protocol for FET, more injections of GnRHa had no more advantages in pregnancy outcomes, on the contrary, it might increase the early miscarriage rate.

Murine models of advanced maternal age: a systematic review and meta-analysis.

Animal models have been developed to aid understanding of the increased incidence of adverse pregnancy complications observed in women of advanced maternal age (AMA). This systematic review of murine models of AMA demonstrates consistent effects of decreased litter size and fetal weight; this supports the future use of these models to determine pathophysiological mechanisms and test therapeutic strategies to improve poor pregnancy outcomes in AMA. Advanced maternal age (AMA; ≥35 years of age) is associated with an increased risk of adverse pregnancy outcomes. To explore causes of adverse pregnancy outcomes in AMA, and to test candidate therapies, an increasing number of murine AMA models have been developed. The aim of this study was to systematically review the literature to assess whether murine AMA models demonstrate a reproducible effect on pregnancy outcomes. PubMed, Ovid, Web of Science and Google Scholar were searched. Studies that reported on pregnancy outcomes in AMA mice and rats were included; the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool evaluated the risk of bias. Eleven mouse and six rat studies were included. AMA mice and rats had reduced litter size (standardised mean difference (SMD): -1.59, 95% confidence interval (CI): -1.84, -1.34 for mice; SMD: -1.66, 95% (CI): -2.09, -1.23 for rats) and reduced fetal weight (SMD: -0.87, 95% CI: -1.24, -0.49 for mice; SMD: -1.05, 95% CI: -1.40, -0.69 for rats). Placental weight was increased in AMA mice (SMD: 0.62, 95% CI: 0.16, 1.08). Subgroup analysis indicated that C57Bl/6 mice had less heterogeneity than other, mostly outbred, mouse strains with regards to litter size (C57 strain I2 = 68.2% vs other strain types I2 = 85.7%). The risk of bias was high, mostly due to the lack of methodological detail and unclear reporting of findings. Murine models of AMA demonstrate similar adverse pregnancy outcomes to those observed in large human epidemiological studies. The reproducible phenotypes in AMA murine models allow the exploration of mechanisms underpinning poor pregnancy outcomes and the pursuit of therapeutic interventions.

P-524 Fertility and subsequent pregnancy outcomes among women with tubal ectopic pregnancy treated with methotrexate

Abstract Study question What are the future fertility prospects and subsequent pregnancy outcomes among women with tubal ectopic pregnancy treated with methotrexate? Summary answer Pregnancy post-ectopic pregnancy occurred in 53% of women within 12 months following methotrexate treatment. Among those who became pregnant, ectopic pregnancy recurrence occurred in 16.8%. What is known already Concerns regarding ectopic pregnancy recurrence and future fertility predominate when counselling women about management options for tubal ectopic pregnancy treatment. Current UK National Institute for Health and Care Excellence guidance is based on low quality evidence and estimate long-term ectopic pregnancy recurrence rate of ∼18.5%. Further, they state that there are no differences in rates of subsequent pregnancy or ectopic pregnancy recurrence between ectopic pregnancy management methods. However, 30% of women managed with methotrexate experience treatment failure and require rescue surgery and subsequent pregnancy outcomes in this group are poorly understood. Study design, size, duration The data for this study were derived from a UK multicentre RCT of methotrexate and gefitinib versus methotrexate and placebo for treatment of ultrasound diagnosed definite or probable tubal ectopic pregnancy with pre-treatment hCG ≥1000 IU/L and ≤5000 IU/L (GEM3). The trial found adding gefitinib to methotrexate was not superior to placebo. This analysis reports trial participant follow-up data at 12-months examining post-treatment fertility, subsequent pregnancy outcomes and participant characteristics associated with ectopic pregnancy recurrence. Participants/materials, setting, methods Trial participants of GEM3 (as described above). Participants were contacted to provide follow-up data 12 months after randomisation to treatment. Where telephone contact was unsuccessful, electronic health records were reviewed to collect pregnancy outcome data. Post-treatment fertility and pregnancy outcomes were summarised using descriptive statistics and compared between groups using a chi-squared test, p&amp;lt;.05 signified statistical significance. Main results and the role of chance Pregnancy follow-up data was obtained for 283/327 trial participants. (167 participants were successfully contacted by telephone; the electronic health records were reviewed for 116 participants). 52.7% (149/283) of the trial participants became pregnant in the 12-month follow-up period. There was no difference in subsequent pregnancy rates between ‘methotrexate only’ and ‘methotrexate and rescue surgery’ groups. The surgical approach (salpingectomy vs salpingotomy) did not affect subsequent pregnancy rates. Among women who had a pregnancy in the follow-up period, a live birth was recorded in 65% of women (n = 93/142, n = 7 missing), any pregnancy loss (miscarriage, ectopic pregnancy, stillbirth, termination of pregnancy or molar pregnancy) was recorded in 43% of women (n = 59/137, n = 12 missing). Recurrent ectopic pregnancy was reported in 16.8% of women (n = 22/131, n = 18 missing). There was no difference in rates of live birth, pregnancy loss or recurrent ectopic pregnancy between methotrexate only and methotrexate and surgery groups or between type of surgical management groups (salpingectomy vs salpingotomy). Limitations, reasons for caution This study only reports on a 12-month follow-up period and this should be considered when interpreting comparatively low post-treatment pregnancy rates. We did not record which couples were trying-to-conceive post treatment and were therefore unable to stratify results by this variable or report subfertility rates. Wider implications of the findings This prospective dataset strengthens current understanding of the likelihood of ectopic pregnancy recurrence. Furthermore, it provides reassurance that women with tubal ectopic pregnancy managed with methotrexate requiring rescue surgery have similar post-treatment fertility and pregnancy outcomes to those successfully treated with methotrexate. Trial registration number ISRCTN67795930

P-511 Prolonging the time of vaginal progesterone supplementation does not improve pregnancy outcomes after day 6 blastocyst transfer

Abstract Study question Does the administration of vaginal progesterone for 6 days improve pregnancy outcomes when transferring day 6 blastocysts, as opposed to 5 days of progesterone treatment? Summary answer We observed similar pregnancy outcomes after 5 and 6 days of vaginal progesterone supplementation following day 6 blastocyst transfer in oocyte recipient cycles. What is known already Progesterone administration promotes the final phase of endometrial preparation for embryo transfer. However, the optimal duration of progesterone transformation still remains unknown. The implantation potential of blastocysts formed at different timepoints is also contentious, as blastocysts on day 6 have been linked to poorer clinical outcomes compared to their day 5 counterparts. It is unclear whether this effect stems from an intrinsic impaired implantation capacity of slow-developing blastocysts, or a displaced window of implantation (WOI). It has been hypothesized that 6 days of progesterone administration may improve clinical outcomes after frozen day 6 blastocyst transfer. Study design, size, duration Retrospective cohort study of oocyte recipients undergoing single day 6 blastocyst transfer, between January 2020 and December 2022. This study compared two groups: day 6 blastocysts transferred after 5 days of progesterone administration (n = 284) and day 6 embryo transfers performed after 6 days of progesterone administration (n = 69). Participants/materials, setting, methods Our study included oocyte recipients who underwent a single embryo transfer of a day 6 blastocyst and hormonal replacement treatment for endometrial preparation with vaginal external progesterone administration (800mg/24h) for either 5 or 6 days prior to embryo transfer. Outcomes were analyzed using unpaired t-test or Fisher’s test and logistic regression. Multivariate models were adjusted for oral or transdermal estrogen administration and endometrial thickness on the day of embryo transfer. P-values &amp;lt;0.05 were considered significant. Main results and the role of chance Mean maternal age was 43.5 years, while patients had a mean BMI of 25.1. Mean days of estrogen therapy prior to embryo transfer were 22.4, with 75.3% of patients using transdermal estrogen administration, and achieving a mean endometrial thickness of 9.6 mm on the day of transfer. Mean progesterone levels on the day of transfer were 11.9 ng/ml. Thirty-seven percent of the day 6 blastocysts were of high quality. None of the demographic or cycle characteristics were significantly different between the study groups. When considering outcomes of day 6 blastocyst transfers, we found no significant differences in biochemical (26.33% vs 20.13%, p = 0.343), clinical (22.06% vs 17.46%, p = 0.49) and ongoing (14.64% vs 9.52%, p = 0.41) pregnancy rates between 5 and 6 days of progesterone administration. Our adjusted analysis further corroborated these results. Limitations, reasons for caution The retrospective nature of the study and low number of transfers performed after 6 days of progesterone treatment warrant careful interpretation. This study only evaluated endometrial preparation by vaginal progesterone administration in oocyte recipients and cannot be extrapolated to other routes of progesterone administration or other patient populations. Wider implications of the findings Poorer reproductive outcomes associated with the transfer of day 6 blastocysts appear to be related to a reduced implantation capacity of slow-developing embryos rather than a displaced WOI due to rising progesterone. WOI appears wider than assumed, as prolonged progesterone transformation times had no effect on pregnancy outcomes. Trial registration number Not applicable

P-586 Adding letrozole to gonadotropins during ovarian stimulation for IVF results in a similar cumulative live birth rate at lower costs following a failed IVF cycle

Abstract Study question Following a failed IVF cycle, does adding letrozole for the first 5 days of a repeated cycle have any advantage versus repeating the same protocol? Summary answer Following a failed IVF cycle, letrozole supplementation during ovarian stimulation for IVF results in a similar cumulative live birth rate (CLBR) with 22% less gonadotropins. What is known already Letrozole results in an increase of intraovarian androgen concentration, which augments follicular stimulating hormone (FSH) receptor expression on granulosa cells and follicular responsiveness to exogenous gonadotropins. Letrozole co-treatment with gonadotropins during controlled ovarian stimulation (COH) for IVF has been investigated mainly in poor and normo-responders with conflicting clinical outcomes. This is the first and largest study that investigates the effects of adding letrozole for the first five days of COH for IVF, in GnRH antagonist cycles, to a category of patients who had a prior failed stimulated IVF cycle using the same protocol. Study design, size, duration This is retrospective monocentric study of 426 patients, with a prior failed stimulated IVF cycle using an antagonist protocol, who underwent a second cycle between 2012 and 2017. In those patients, we studied the clinical outcomes of doing a repeated cycle, using the same protocol with the addition of 5mg of letrozole daily in the first 5 days of the cycle (Group A, N = 213) versus doing a repeated similar cycle without letrozole (Group B, N = 213). Participants/materials, setting, methods Groups A and B were matched for age, body mass index, anti-mullerian hormone and infertility diagnosis. Statistical analyses were carried out using student t test, Anova and linear regression models. The primary outcome was the CLBR. Secondary outcomes included the number of mature follicles, the number of mature oocytes (MII), the number of usable embryos, clinical pregnancy rates (CPR), live birth rates (LBR) and the total dose of gonadotropins administered. Main results and the role of chance This is the first study that investigates the effects of co-treatment with letrozole during COH for IVF in the category of patients who had a prior failed IVF cycle. Our results show that patients who received letrozole during COH with gonadotropins, versus gonadotropins alone, had a significantly lower number of MII oocytes (7±4.6 vs 8,2±5.0; P &amp;lt; 0.01). However, despite that, they had a similar number of usable embryos (1.8±1.6 vs 1.9±1.7; P = 0.31), CPR (23.5% vs 28.7%; p = 0.22), LBR per embryo transfer (16.9% vs 22.1%; p = 0.17) and CLBR (27.8% vs 25.3%; p = 0.55). A 22% lower dose of gonadotropins (3468±1389IU vs 4442±1657IU; p &amp;lt; 0.001) was needed to achieve similar pregnancy outcomes in the letrozole group versus the control group, resulting in lower treatment costs. Limitations, reasons for caution The retrospective nature of this study is its main limitation. Wider implications of the findings This study confirms that in women with a prior failed IVF cycle, co-treatment with letrozole results a similar cumulative live birth rate at a significant lower cost. Trial registration number NCT05677828

P-281 Single-cell RNA sequencing analysis of granulosa cells in preovulatory follicles in normal ovarian reserve patients undergoing progestin-primed ovarian stimulation and GnRH-antagonist

Abstract Study question Could the difference in controlled ovarian stimulation protocol between progestin-primed ovarian stimulation and GnRH-antagonist induce change in the expression genes of human granulosa cells? Summary answer The mitochondrial DNA (mtDNA) gene expression of granulosa cells in patients who underwent progestin-primed ovarian stimulation was significantly higher than the GnRH-antagonist. What is known already The progestin-primed ovarian stimulation (PPOS) protocol has attracted attention and many studies have reported similar pregnancy outcomes for both PPOS and the GnRH-antagonist (GnRH-ant). However, our previous study demonstrated that pregnancy rate was significantly lower in PPOS compared to GnRH-ant (38th Hybrid Annual Meeting of the ESHRE, O-130). In this study, we evaluated the gene expression of granulosa cells (GCs) which affects reproductive outcome. Many studies have shown a close association between the mitochondrial status of GCs and embryo’s quality. To date, the change in gene expression of GCs with different controlled ovarian stimulation protocols have not been investigated. Study design, size, duration From November 2021 to January 2022, all samples were obtained from the patients who provided written informed consent before the inclusion and underwent controlled ovarian stimulation cycles at a single-institution. Single cell RNA-seq (scRNA-seq) was performed on 2,224 cells corresponding to GCs of the MII-oocyte follicles from a total of 16 patients with normal ovarian reserve (aged &amp;lt; 40 years, AMH ≧1.1 ng/mL) undergoing PPOS with chlormadinone acetate (n = 8), or GnRH-ant with cetrorelix (n = 8). Participants/materials, setting, methods The GCs were obtained by follicular aspiration from 16 patients undergoing oocyte retrieval. The follicular fluid (FF) from each follicle was collected and all FF were mixed together in MII-oocyte for sequencing. The GCs were isolated from the blood cells and cellular debris using Percoll gradient centrifugation. Samples for sequencing were prepared using Chromium Next GEM Single Cell V(D)J Reagent Kits. Libraries were sequenced in DNBSEQ-G400, and reads processed with CellRanger and visualized with CellxGene. Main results and the role of chance Two population of GCs were used in this investigation: PPOS and GnRH-ant of MII-oocyte. After the quality control, 1,197 cells for PPOS and 1,027 cells for GnRH-ant, respectively, were analyzed. The GCs of MII-oocyte were clustered into 6 groups based on Leiden algorithm and visualized by UMAP analysis. There was no significant difference in the gene expression and cell distribution in each cluster. In the two population of GCs, we identified 12 differentially expressed genes (DEGs). Interestingly, we observed significant increase in expression of mtDNA genes in PPOS of MII-oocyte as compared to GnRH-ant of MII-oocyte. The data were confirmed by qRT-PCR analysis. Limitations, reasons for caution Our conclusions are limited due to the inclusion of Asian patients at a single-institution. The results need to be validated across different centers and other ethnicities. Due to the small sample size, these results should prompt further study to confirm our findings. Wider implications of the findings These findings describe, for the first time, the DEGs of GCs investigated in different COS protocols at single-cell level. This study suggests that progestin for PPOS induce elevation of the mt DNA gene expression of GCs which may be associated with reproductive outcomes. Trial registration number Not applicable

Comparison of Combination-Vaginal Clindamycin with Oral Metronidazole and Oral Metronidazole Alone in the Treatment of Bacterial Vaginosis

Introduction: Bacterial vaginosis is the most common vaginal infection of sexually active woman. Bacterail vaginosis has been associated with preterm labour, amniotic fluid infection, chorioamniotiss and postpartum endometritis. Objective: To compare the efficacy of combination oral metronidazole-vaginal clindamycin gel with oral metronidazole alone in the treatment of bacterial vaginosis. Material and methods: This Randomized Controlled Trial was conducted in Gynaecology and Obstetrics Department, District Headquarter Hospital, Faisalabad. Approval from hospital Ethical Review Committee was taken after formulation of synopsis. 422 Patients fulfilling the inclusion criteria enrolled in the study. Informed consent was taken from each participant of the study. Patients was randomized into Group A and Group B using computer generated random number table. Results: Data was collected from 422 patients with mean gestational age 38.67 ± 1.69 weeks. The cumulative cure rate in the oral metronidazole group was 87% and 89.6% in the oral clindamycin group. There was no statistical difference in the efficacy of the two medications (p = 0.639). Nine (13%) of the women who received oral metronidazole and seven (10.4%) of the women in the oral clindamycin group had treatment failures following the test of cure, with an overall failure rate of 11.8%. Conclusion: It is concluded that both medications have comparable efficacy and similar pregnancy outcomes in the treatment of bacterial vaginosis. Keywords: Vaginosis, Prevalence, Woman, Postpartum