Early Pregnancy Loss Rate Research Articles

Outcomes for Female Physicians Compared With Nonphysicians After Assisted Reproductive Technology.

To evaluate outcomes of female physicians after assisted reproductive technology (ART). We conducted a retrospective cohort study using data from 248 physician patients and 3,470 nonphysician patients who underwent a total of 10,095 fresh or frozen ART cycles at a single academic center in an insurance-mandated state between January 2015 and March 2022. The primary outcome was live-birth rate. The secondary outcomes were implantation rate, early pregnancy loss rate, and time to pregnancy. Models were adjusted for confounders where appropriate. Both groups were similar in age (mean physician age 36.29 years; mean nonphysician age 35.96 years, P=.35). Physicians had lower body mass index (BMI) (mean physician BMI 23.51, mean nonphysician BMI 26.37, P<.01), and a higher proportion were diagnosed with unexplained infertility (physician 33.9%, nonphysician 25.9%, P<.01) and used preimplantation genetic testing for aneuploidy (physician 21.5%, nonphysician 12.7%). Physicians and nonphysicians had similar live-birth rates (physician 39.3%, nonphysician 38.2%; adjusted relative risk [aRR] 1.01 95% CI, 0.91-1.13), implantation rates (physician 34.7%, nonphysician 33.7%; relative risk 1.03 95% CI, 0.94-1.14), and early pregnancy loss rates (physician 21.9%, nonphysician 19.8%; aRR 1.18 95% CI, 0.99-1.41) per transfer. Physicians had a shorter time from initial ART cycle to pregnancy (physician 21.82 weeks, nonphysician 25.16 weeks; aRR 0.86, 95% CI, 0.83-0.89). There was no difference between female physicians and nonphysicians in assisted reproduction cycle outcomes. Physicians become pregnant slightly faster than nonphysicians.

Association between subchorionic hematoma in the first trimester and outcomes of singleton pregnancies achieved through assisted reproductive technology: a systematic review and meta-analysis.

To evaluate the association between first trimester (≤ 12 weeks gestation) subchorionic hemorrhage (SCH), and maternal and neonatal outcomes in women who conceived with the help of assisted reproductive technique (ART). PubMed, Embase, Web of Science, and Scopus databases were searched for observational studies that specifically focused on women who achieved pregnancy via ART and investigated the relationship between early pregnancy (within 12 weeks of gestation) SCH and maternal and neonatal outcomes. Only studies with singleton pregnancies and reporting data on the comparator group (women without SCH) were included. Primary outcomes of interest included incidences of early (within 20 weeks of gestation) pregnancy loss, preterm delivery, caesarean section, and live birth rates. Pooled effect sizes were reported as odds ratio (OR) with 95% confidence intervals (CI). Nine studies were included. All studies had a cohort design. In all studies, the primary assisted reproduction technique used was in-vitro fertilization (IVF). Compared to pregnancies without SCH, women with diagnosed early pregnancy SCH have a similar risk of preterm birth (< 37 weeks) (OR 1.01, 95% CI 0.83, 1.22), low birth weight (< 2500 g) (OR 1.01, 95% CI 0.59, 1.73) and fetal growth restriction (OR 1.57, 95% CI 0.62, 4.02). The gestational age (in weeks) (weighted mean difference (WMD) - 0.06, 95% CI - 0.18, 0.06) and the birth weight (in grams) (WMD - 16.5, 95% CI - 62.9, 29.8) were also similar in the two groups. The odds of early pregnancy loss (OR 1.39, 95% CI 0.97, 2.01), live birth (OR 0.77, 95% CI 0.55, 1.08) and caesarean delivery (OR 0.97, 95% CI 0.81, 1.16) were statistically similar in both groups. The risk of maternal adverse outcomes such as gestational diabetes (OR 0.98, 95% CI 0.74, 1.29), hypertensive disorder (OR 0.95, 95% CI 0.63, 1.43), premature rupture of membranes (PROM) (OR 1.36, 95% CI 0.90, 2.05) and placental abruption (OR 2.44, 95% CI 0.57, 10.5) was also similar in both the groups. There was no evidence of publication bias. The findings suggest that SCH may not significantly increase the risk of adverse maternal and perinatal outcomes in pregnancies conceived through ART, particularly IVF. PROSPERO registration number CRD42024533996.

A retrospective analysis of sheep generated by somatic cell nuclear transfer

Somatic cell nuclear transfer (SCNT) is one of the primary methods for production of genetically engineered sheep, which allows for gene editing or transgene introduction in somatic cells. The use of SCNT eliminates the risk of genetic mosaicism in embryos and animals that is commonly observed after zygote micromanipulations. This retrospective analysis of SCNT in sheep performed at Utah State University, spanning from 2016 to 2021, examined parameters that may impact pregnancy and full-term development, including donor oocytes (donor age), donor cell lines, SCNT parameters (time of oocyte activation following SCNT, number of transferred embryos, in vitro maturation and culture conditions), and recipients (surgical number and ovulatory status), as well as factors that may correlate with large offspring syndrome or abnormal offspring syndrome (LOS/AOS) in the fetuses and lambs. Our findings indicated that compared to prepubertal oocytes, the SCNT embryos produced from adult sheep oocytes had comparable in vitro maturation rates, pregnancy and full-term development rates, as well as SCNT efficiency. In addition, earlier activation time of SCNT embryos (e.g. 24–26 h post maturation) was correlated to the early pregnancy loss rate, full-term rate, and SCNT efficiency. Compared to our standard serum-containing medium, commercial serum-free culture medium showed a positive correlation with the full-term development of sheep SCNT embryos. Transferring 15–30 embryos per recipient resulted in consistently good pregnancy rates. Surgical numbers and ovulatory status (having at least one follicle between 6 and 12 mm in size or a corpus hemorrhagicum (CH)) of recipients did not affect pregnancy and full-term development rates. In summary, this retrospective analysis identified parameters for improving pregnancy and full-term development of SCNT embryos in sheep.

P-384 The risk of early pregnancy loss following medicated frozen embryo transfer

Abstract Study question Do exogenous gonadocorticoids protect against early pregnancy loss (EPL) following frozen embryo transfer (FET)? Summary answer Exogenous gonadocorticoids conferred a 59.5% increased risk of EPL (p&amp;lt;.05) without any advantage to biochemical pregnancy rates. This corresponded to a significantly thinner pre-FET endometrium. What is known already During a medicated FET cycle, exogenous progestogens and/ or oestrogens are administered with the intention of inducing endometrial maturation prior to implantation. However, the concomitant administration of both these gonadocorticoids is known to produce secretory changes alongside endometrial proliferation. It is unclear whether this non-physiological morphology is truly favourable for implantation, with some authors reporting similar EPL rates between medicated and “natural” FET cohorts while others have found exogenous gonadocorticoids to reduce the risk of EPL compared to alternative protocols. Study design, size, duration Retrospective, single-centre cohort study assessing the rates of biochemical pregnancy and EPL following 819 FETs. All FETs were conducted between January 2019 and November 2022 within a single British centre. Participants were followed up at 6-8 weeks post-FET to assess for biochemical pregnancy and EPL. The former was defined as a positive urinary human chorionic gonadotropin; the latter was defined as the absence of pregnancy on transvaginal ultrasound despite previous confirmation of biochemical pregnancy. Participants/materials, setting, methods Participants comprised 586 women undergoing medicated FET cycles and 233 women undergoing “natural” cycles. Electronic healthcare records (EHRs) were accessed to record pregnancy outcomes, hormonal therapies and endometrial thickness at 48hrs prior to FET. Binomial variables were compared using Pearson’s chi-squared test; continuous variables were analysed via T-tests and logistic regressions. Cut-offs of 8mm, 9mm and 10mm were applied to endometrial thickness in sub-group analyses. Statistical test were conducted using STATA v18.0 (StataCorp LLC, Texas). Main results and the role of chance Women undergoing medicated FET cycles achieved 16.9% higher rates of biochemical pregnancy compared to women undergoing “natural” cycles (57.7% versus 49.4%, p&amp;lt;.05). However, they also suffered a 59.5% higher rate of EPL (28.8% versus 18.0%, p&amp;lt;.05), which corresponded to significantly thinner endometrium at pre-FET ultrasound in comparison to women on “natural” cycles (9.13mm versus 9.48mm, p&amp;lt;.05). Logistic regressions revealed that, within the medical FET cohort, each 1mm increase in thickness conferred a 13.8% increased risk of EPL (95%CI: 3.1%-25.5% p&amp;lt;.01) but no advantage in biochemical pregnancy rates. “Natural” cycles demonstrated no such association. Endometrial thickness was then dichotomised using three thresholds. Women undergoing medicated FET cycles whose endometrium exceeded 9mm or 10mm had 62.1% and 71.4% greater risk of EPL, respectively, compared to those below either threshold. Biochemical pregnancy rates did not differ. Women undergoing “natural” FET cycles did not exhibit any significant difference using either threshold, suggesting that the disparate EPL rate in medicated cycles may result from non-physiological endometrial stimulation by exogenous gonadocorticoids. The 8mm cut-off was insignificant in both cohorts. Although these results cannot confirm a causal relationship between exogenous gonadocorticoids, endometrial thickness and EPL, they are sufficiently striking to warrant further investigation into their pathophysiological basis. Limitations, reasons for caution EHRs failed to report endometrial thickness for 125 participants (15.3%), limiting statistical power in logistic regressions. Our results cannot be confidently applied to other centres until further studies are conducted. Additionally, our design did not allow for the disparity in EPL rates to be attributed to a particular pathophysiological mechanism. Wider implications of the findings This data generates further uncertainty within the literature with regards to the relative risk of EPL in medicated versus “natural” FET cycles. The empirical evidence to support one protocol over the other is insufficient at present, and thus clinical recommendations should be based on the individual preferences of each patient. Trial registration number not applicable

P-134 Fatty acid supplementation during warming improves pregnancy outcomes after frozen blastocyst transfers: a propensity score-matched study

Abstract Study question Does warming with fatty acids (FAs) affect the viability of human blastocysts and pregnancy outcomes after a single vitrified-warmed blastocyst transfer (SVBT)? Summary answer FA-supplemented warming solutions promoted the blastocyst outgrowth by decreasing the degeneration of trophoblast cells and improved pregnancy outcomes after SVBTs. What is known already Vitrification is considered a well-established technique and has been used worldwide. However, previous studies demonstrated the detrimental effects of vitrification on pre-implantation development and term pregnancy in oocytes and embryos. Vitrification reduces the intracellular lipid content and decreases the competence for pre-implantation development. The FA supplementation into the warming solution restores the lipid content in the ooplasm and improves developmental competence by promoting the β-oxidation pathway in mice. Although, in humans, the FA-supplemented warming solutions reportedly improved pregnancy outcomes after vitrified-warmed cleavage-stage embryo transfers, the effectiveness of these solutions on blastocyst warming remain unclear. Study design, size, duration The experimental study included 401 discarded blastocysts. The blastocysts were warmed using the FA-supplemented (FA group) or non-supplemented (control group) solutions. The blastocyst adhesion, outgrowth area, and incidence of outgrowth degeneration were assessed. The retrospective cohort study included 4,426 treatment cycles from 4,426 women who underwent SVBTs between January 2023 and August 2023 (January–May 2023, control group; June–August 2023, FA group). Pregnancy outcomes were compared statistically between the groups. Participants/materials, setting, methods The implantation competence was experimentally examined using an outgrowth model. The blastocysts were placed on fibronectin-coated dishes and cultured for 96 hours. The embryos were designated as degenerated when the outgrowth area decreased by &amp;gt; 10%, compared with the maximum area. For the clinical study, multiple covariates that affected the outcomes were used for propensity score matching. The patients in the FA group were matched with controls using a propensity score in a 1:1 ratio. Main results and the role of chance The adhesion rate after the outgrowth culture was comparable between the control and FA groups. However, the outgrowth was larger in the FA group than in the control group. The multivariate linear regression analysis also demonstrated similar results. Furthermore, the incidence of outgrowth degeneration was significantly decreased in the FA group. Furthermore, the subgroup analyses revealed that FA-supplemented warming solutions were effective in blastocysts donated from young patients, day 5 blastocysts, and morphologically good blastocysts. For the retrospective cohort study, the implantation, clinical pregnancy, and ongoing pregnancy rates were significantly higher in the FA group than in the control group. The multivariate logistic regression analysis also demonstrated that warming with FA-supplemented solutions significantly increased the probability of ongoing pregnancies. However, the rates of early pregnancy loss and miscarriage in the first trimester were comparable between the groups. The subgroup analyses demonstrated a similar trend to in vitro experiments; the FA-supplemented solutions were more effective in good prognosis cases (young patients, day 4/5 blastocysts, and morphologically good blastocysts) than in poor prognosis cases (advanced age patients, day 6/7 blastocysts, and morphologically poor blastocysts). Limitations, reasons for caution This was a single-centre, retrospective study, necessitating further multicentre studies to ascertain the generalizability of these findings to other clinics with different protocols and/or patient demographics. Despite using propensity score matching and multivariate models to adjust for the confounders, we cannot adjust for all possible confounders. Wider implications of the findings FA-supplemented warming solutions improved pregnancy outcomes after SVBTs, particularly in patients with a good prognosis. These warming solutions could contribute to maximizing clinical outcomes, shortening treatment periods, and reducing patient burden. Trial registration number not applicable

O-205 Dydrogesterone versus micronized vaginal progesterone for luteal phase support in hormone replacement therapy frozen embryo transfer cycles (REMODEL): an exploratory randomized controlled trial

Abstract Study question Is dydrogesterone (DYD) comparable to micronized vaginal progesterone (MVP) for luteal phase support (LPS) in hormone replacement therapy frozen embryo transfer (HRT-FET) cycles? Summary answer Ongoing pregnancy rates (OPR) at 12 weeks’ gestation were comparable between the study group using DYD and the control group using MVP. What is known already Thanks to vitrification, the number of frozen embryo transfer cycles has significantly increased, prompting for a thorough optimization. Few studies have prospectively compared different progesterone regimens in artificial frozen embryo transfer cycles. Currently, MVP is most commonly used for LPS in this setting, but side effects such as vaginal discharge cannot be neglected. Dydrogesterone, a selective progesterone receptor agonist with a high oral bioavailability, could be considered due to its more patient-friendly administration. Two randomized controlled trials confirmed the non-inferiority of dydrogesterone to MVP for LPS in fresh cycles, but robust data on its use in HRT-FET cycles remain limited. Study design, size, duration An exploratory randomized controlled trial was conducted at a university hospital from October 2021 to September 2023. Subjects were randomly allocated 1:1 to the study group using DYD (10mg three times daily) for LPS or the control group using MVP (2x200mg twice daily), all performing FET in a HRT cycle. The primary outcome was ongoing pregnancy rate at 12 weeks (OPR). Secondary objectives included biochemical pregnancy loss, early pregnancy loss (EPL) and live birth rate. Participants/materials, setting, methods Patients under 41 years of age with a normal BMI undergoing a single blastocyst transfer in a HRT-FET cycle without endometrial abnormalities were eligible for inclusion. Patients who required more than 14 days of estradiol valerate priming (2mg three times daily) to achieve an endometrial thickness of at least 7 mm were not included. Of the 170 patients screened, 19 did not meet the randomization criteria and 3 withdrew after randomization. Main results and the role of chance Demographic characteristics such as age, BMI, cause of infertility and regular cycle were comparable between the study and control groups, as were the frozen transfer cycle characteristics. With three drop-outs after randomization, both a per-protocol (PP) and an intention-to-treat (ITT) analysis were performed for the primary outcome. According to the PP analysis, the OPR was 31.5% in the study group and 45.3% in the control group (p = 0.08, difference in proportions (%) -14, 95% CI: -39-11). The ITT analysis showed similar results (OPR 31.1% versus 44.2% in the study and control groups, respectively, p = 0.10). Multivariate regression adjusting for age, BMI, endometrial thickness and parity showed no significant association between the type of LPS administered and OPR (OR 1.92, 95% CI 0.95-3.86, p = 0.07). Positive hCG rates were comparable between both groups (58.9% versus 61.3% in the study and control groups, p = 0.76). Differences in biochemical pregnancy loss (14.0% versus 2.2% in the study and control groups, respectively, p = 0.05) and EPL (32.6% versus 23.9% in the study and control groups, respectively, p = 0.37) did not reach statistical significance. The live birth rate did not differ significantly between the two groups (26.8% versus 41.9%, p = 0.06), but the delivery outcome of 3 patients is missing to date. Limitations, reasons for caution Despite the randomized nature of the study, the exploratory design warrants cautious interpretation of the results due to the primary outcome’s insufficient statistical power. The dosages of the LPS medication used are based on common clinical practice, but due to the absence of dose-finding studies, this may impact the results. Wider implications of the findings The results, although not statistically significant, may raise clinical implications and call for larger studies. A forthcoming analysis will assess progesterone levels throughout the cycle in these study patients, examining their impact on pregnancy outcomes. Given differences in pharmacological profiles, various dosages may also be explored. Trial registration number NCT04758871

P-663 Comparing clinical outcomes in PGT-A cycles using donated oocytes between progesterone and GnRH-antagonist protocols

Abstract Study question Does Progesterone Primed Ovarian Stimulation (PPOS) demonstrate comparable efficiency to the GnRH-antagonist protocol in terms of laboratory/reproductive outcomes in PGT-A cycles with donated oocytes? Summary answer PPOS demonstrates efficiency in PGT-A cycles with donated oocytes, comparable to the GnRH-antagonist protocol, providing cost-effectiveness and enhanced donor comfort. What is known already The demand for TRA cycles with donated oocytes steadily rises each year. This treatment instills high hopes for success. Ongoing advancements in donor stimulation protocols prioritize safety and comfort. The shift from LH agonist to antagonist suppresses LH peaks, and recently, PPOS has joined, offering a more comfortable, cost-effective, and equally safe alternative with fewer ultrasound checks, mitigating ovarian hyperstimulation syndrome. Study design, size, duration Retrospective assessment of an oocyte donor cohort undergoing ovarian stimulation: 182 cycles with the GnRH-antagonist protocol (Group 1: G1) and 120 with PPOS (Group 2: G2), conducted between July 2017 and June 2023. Ovarian stimulation involved 225 IU/d of FSHr or FSHu, triggering with a GnRH agonist, and subsequent biopsy of evolutionarily robust embryos after extended culture. Both fresh and vitrified oocytes, inseminated with either self or donor sperm, were included. Participants/materials, setting, methods We analyzed 1188 embryos (G1: 676; G2: 512). Trophoectoderm biopsies from D5/D6 blastocysts underwent NGS using the Illumina platform (VeriSeq Illumina®, San Diego, CA, USA). Comparison included total and MII oocyte numbers, fertilization rates, viable embryos, euploid/aneuploid embryos, mosaic embryos, and clinical outcomes: biochemical pregnancy (BPR), biochemical pregnancy loss (BPLR), clinical pregnancy (CPR), early pregnancy loss (EPLR), ongoing pregnancy (OPR), and live birth (LBR) rates. Statistical analyses were carried out using R statistical software (v.4.3.1). Main results and the role of chance The mean ages of donors (25.57±4.05) and recipients (41.82±4.06) were comparable in both groups. The male partner’s age differed (G1: 40.47±7.87; G2: 42.34±7.65) (p = 0.019). Results were adjusted for confounding factors, including recipient and donor ages, oocyte and seminal origin, and male factor variables. Ovarian stimulation duration (9.26 days), total gonadotropin dose (2015.64 IU), and oocyte origin (fresh G1: 69.8 %; G2: 62.5 %; vitrified G1: 30.2 %; G2: 37.5 %) showed equivalence. Statistical significance emerged in total oocytes retrieved (G1: 17.92±7.64; G2: 20.23±7.89) (p = 0.008), mean microinjected MII (G1: 10.25±1.79; G2: 10.07±1.36) (p = 0.040) and fertilization rate (G1: 73.98 %; G2: 79.44 %) (p = 0.001). The usable embryo rate was similar (G1: 54.78 %; G2: 54.47 %). Significant differences arose in mean biopsied embryos/cycle (G1: 3.71; G2: 4.27) (p = 0.016), but not for aneuploid embryos (G1: 29.71 %; G2: 29.49 %) (p = 0,998). Biochemical pregnancy rates were significant (G1: 48.8 %, G2: 60.4 %) (p = 0.022). Other clinical parameters showed no differences, with LBR at 35.5 % in G1 and 37.8 % in G2 (p = 0.752). Limitations, reasons for caution The study is retrospective, where we addressed potential biases by incorporating confounding variables. However, to confirm our initial findings, randomized prospective studies with an appropriate sample size are essential. Wider implications of the findings In egg donation cycles, PPOS shows optimal embryonic performance resulting in a live birth rate comparable to the GnRH antagonist protocol. Additionally, it offers cost-effectiveness and enhanced comfort for donors. Trial registration number Not applicable

Clinical outcomes of fresh and frozen embryos transfer after in vitro fertilization in spouses of patients with severely low sperm concentration and motility.

To compare the pregnancy and neonatal outcomes of in vitro fertilization-embryo transfer (IVF-ET) with fresh or frozen embryos in spouses of patients with severely low sperm concentration and motility. A total of 2300 patients whose spouses have severely low sperm concentration and motility underwent IVT-ET in the Reproduction Medicine Center, Sir Run Run Shaw Hospital from April 2018 to April 2022. After applying the propensity score matching (PSM), 473 fresh embryo transferred cycles and 473 frozen embryo transferred cycles were selected for the study, and the pregnancy and neonatal outcomes were compared between the two groups. There were no significant differences in pregnancy outcomes and neonatal outcomes between fresh and frozen embryo groups (all P>0.05). In the stratification analysis, the number of retrieved oocytes in the fresh good-quality embryo transfer group was significantly increased compared with the fresh poor-quality embryo group (P<0.05), but the very early pregnancy loss rates were similar between the two groups (P>0.05), while the rate in fresh good-quality embryo transfer group was significantly higher than that in the frozen good-quality embryo transfer group (P<0.05). Among different age groups of women, the number of retrieved oocytes and the level of estrogen in the fresh embryo transfer group was significantly higher in the 20 to <30 years old group than that in the 30 to <35 years old group (both P<0.05), but the clinical pregnancy rate was lower in the 20 to <30 years old group than that in the 30 to <35 years old group (P>0.05). Additionally, the very early pregnancy loss was significantly increased in the fresh embryo group compared with the frozen embryo group in the 20 to <30 years age group (P<0.05). There were no significant differences in pregnancy and neonatal outcomes between fresh and frozen embryo transfer in spouses of patients with severely low sperm concentration and motility undergoing IVF-ET. Due to the shorter transfer times, less embryo freezing damage and reduced costs, fresh embryo transfer can be considered as the first choice. However, it is not necessary to pursue fresh embryo transfer if maternal oestrogen levels are too high and there is a tendency of overstimulation.

Levothyroxine may not adequately prepare hypothyroid women for controlled ovarian hyperstimulation

BackgroundThyroid axis dysregulation during controlled ovarian hyperstimulation (COH) is more pronounced in hypothyroid‐treated women. Whether or not this leads to compromised thyroid hormone levels within the ovarian follicular fluid is not known.AimsTo determine whether ovarian follicular thyroid hormone levels are compromised in adequately replaced hypothyroid women undergoing controlled ovarian hyperstimulation (COH), and/or influence cycle/pregnancy outcomes.Materials and MethodsProspective cohort study involving 46 euthyroid (anti‐thyroid peroxidase antibody negative) and 16 levothyroxine‐replaced women with baseline thyroid‐stimulating hormone (TSH) &lt;2.5 mIU/L attending their first COH cycle. Follicular fluid TSH, free triiodothyronine (T3) and free thyroxine (T4) were recorded at oocyte pick‐up. Serum levels were measured at: (i) baseline; (ii) human chorionic gonadotropin trigger day; and (iii) cycle conclusion. The number of mature oocytes retrieved, fertilisation, early pregnancy loss and live birth rates were compared.ResultsMedian serum TSH levels were similar at baseline (1.76 vs 1.24 mIU/L, P = 0.053), but free T3 levels were lower (4.5 vs 4.8 pmol/L, P = 0.029) in levothyroxine‐replaced compared to euthyroid women, with serum TSH levels increasing across ovarian stimulation (P = 0.006) into pregnancy testing (P = 0.030). Follicular fluid free T3 levels were lower in levothyroxine‐replaced women (median 4.3 vs 4.6 pmol/L, P = 0.032). Fertilisation rates were lower (52% vs 71%, P = 0.043) in women requiring levothyroxine replacement, but numbers of mature oocytes retrieved, early pregnancy loss and live births did not differ.ConclusionAdequately replaced hypothyroid women achieve lower ovarian follicular fluid free T3 levels and poorer fertilisation rates compared to euthyroid women undergoing COH. Optimising T3 levels may be pivotal in improving COH outcomes in hypothyroid women.

Effect of anti-Müllerian hormone on early pregnancy loss in hormone replacement therapy-frozen-thawed embryo transfer cycles: An analysis including 6597 pregnant patients undergoing their first invitro fertilization/intracytoplasmic sperm injection cycle.

To investigate the relationship between anti-Müllerian hormone (AMH) level and early pregnancy loss in patients who underwent their first embryo transfer by hormone replacement therapy-frozen-thawed embryo transfer (HRT-FET) and analyze the threshold effect. A retrospective cohort analysis was performed on pregnant women undergoing HRT-FET at the Reproductive Medical Center of Henan Provincial People's Hospital from January 2016 to December 2021. The patients were divided into four groups based on AMH concentration according to the Poseidon criteria: group A (≤1 μg/L), group B (1-≤2 μg/L), group C (2-≤6 μg/L), and group D (>6 μg/L). Univariate analysis, multivariate logistic regression analysis, smooth curve fitting, and threshold effect analysis were applied to investigate the influence of AMH on the outcome of early pregnancy loss in invitro fertilization/intracytoplasmic sperm injection and HRT-FET cycles. Of the 6597 pregnant women, early pregnancy loss occurred in 893, giving an early pregnancy loss rate of 13.54%. Univariate regression analysis demonstrated that age, female body mass index, AMH, antral follicle count, endometrial thickness at endometrial transformation day, total retrieved oocyte number, number of pregnancies, duration of infertility, type of infertility, and the number of embryos transferred were all factors influencing the early pregnancy loss rate (P < 0.050). Multivariate logistic regression analysis, after adjusting for confounders, further stratified the analysis of patients of different ages. With group A as the control group, the results showed that when age was younger than 35 years, the pregnancy loss rates in groups B, C, and D were lower than that in group A, with statistical significance (P < 0.050); when age was 35 years or older, there was no statistically significant difference in outcome indicators between the groups (P > 0.050). A threshold effect analysis revealed that the AMH threshold was 2.83 μg/L. When the AMH concentration was less than 2.83 μg/L, the early pregnancy loss rate decreased significantly with increasing AMH concentration; the early pregnancy loss rate decreased by 21% for each unit increase in AMH (odds ratio 0.79; 95% confidence interval 0.71-0.88; P < 0.001); when the AMH concentration was 2.83 μg/L or more, there was no statistical difference in the change in early pregnancy loss rate (odds ratio 1.01; 95% confidence interval 0.99-1.03; P = 0.383). For pregnant women after their first embryo transfer, there is a curvilinear relationship between the influences of AMH levels on early pregnancy loss rates in patients younger than 35 years. When the AMH level was less than 2.83 μg/L, the early pregnancy loss rate declined significantly with increasing AMH levels.

Single Euploid Embryo Transfer Outcomes After Uterine Septum Resection

ObjectiveTo study pregnancy outcomes after single euploid embryo transfer (SEET) in patients who underwent prior uterine septum resection to those with uteri of normal contour, without Müllerian anomalies or uterine abnormalities including polyps or fibroids, and without a history of prior uterine surgeries. DesignRetrospective cohort study SettingSingle academic affiliated center Patients60 cycles of patients with prior hysteroscopic uterine septum resection who underwent an autologous SEET between 2012-2020 were used as the investigational cohort. A 3:1 ratio propensity score matched control cohort of 180 single euploid embryo transfer cycles from patients without a history of uterine septa were used as the control group. Intervention(s)No interventions administered. Measurements and Main ResultsPregnancy, clinical pregnancy loss, ongoing clinical pregnancy, and live birth rates in patients with history of uterine septum resection compared to matched patients without Müllerian anomalies or uterine surgeries. Patients with a prior uterine septum had significantly lower rates of chemical pregnancy (58.33% vs 77.2%, p=0.004), implantation (41.67% vs 65.6%, p=0.001), and live birth (33.33% vs 57.8%, p=0.001) per transfer. No statistical difference in clinical pregnancy loss rates was found when comparing septum patients with controls (8.33% vs 7.8%, p=0.89). ConclusionPatients with history of hysteroscopic resection who undergo in vitro fertilization are more susceptible to suboptimal clinical outcomes compared to patients with normal uteri. Early pregnancy loss rates in patients with a uterine septum are higher than in those without, however, after resection, the rates are comparable. Patients born with septate uteri require assessment of surgical intervention prior to SEET and to optimize their reproductive outcomes.

A randomized, controlled clinical study of low-molecular-weight heparin improving pregnancy outcomes in PCOS women undergoing IVF: study protocol

BackgroundPolycystic ovary syndrome (PCOS), an incidence of 10–15% in women of reproductive age, shows sex hormone disorders, luteal insufficiency, and the tendency of placental villus space thrombus. The incidence of early pregnancy loss in women with PCOS is three to eight times higher than that in non-PCOS women. PCOS women were reported in a pre-thrombotic state, which was manifested by accelerated thrombin production, increased PAI-1 activity, and fibrinogen. Other research also found an over-activated state of women with PCOS in immune system. Therefore, changing the prethrombotic state of PCOS through anticoagulation may be a new way to improve the adverse pregnancy outcome of PCOS. Low-molecular-weight heparin (LMWH) is the most common used anticoagulant drug in pregnancy, and it also was proposed for the prevention of recurrent abortion, although the application of LMWH in PCOS population during early pregnancy has not been reported. The objective of this study is to investigate the effect of LMWH on pregnancy outcomes after invitro fertilization-frozen embryo transfer (IVF-FET) in patients with polycystic ovary syndrome.MethodsA total of 356 PCOS women aged between 20 and 38 years which prepared for IVF followed with FET will be enrolled in the study. The patients, from four different hospitals stratified by age and body mass index (BMI), will be randomly divided into the study group who will be treated with LMWH started on the day of progesterone transformation (hormone therapy) during FET cycle and the control group without additional medicine. Serum or urine hCG test will be given 14 days after embryo transfer to confirm biochemical pregnancy. If pregnancy is positive, LMWH+ hormone therapy/hormone therapy will be continued for another 2 weeks. Transvaginal ultrasonography will be performed 14 days later to confirm intrauterine pregnancy. The primary outcome is the ongoing pregnancy, which is defined as intrauterine live fetus with ultrasound after 12 weeks of gestation.DiscussionThis is the first study protocol to investigate the efficacy of LMWH as an adjuvant drug for IVF-FET outcomes in PCOS women, by comparing differences in ongoing pregnancy rate, clinical pregnancy rate, live birth rate, and early pregnancy loss rate between LMWH group and the control group.Trial registration ClinicalTrials.gov ChiCTR2000036527. Registered on August 24, 2020

Clinical outcomes of preimplantation genetic testing for aneuploidy in high-risk patients: a retrospective cohort study.

The purpose of this study was to evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on clinical outcomes among high-risk patients. This retrospective study involved 1,368 patients and the same number of cycles, including 520 cycles with PGT-A and 848 cycles without PGT-A. The study participants comprised women of advanced maternal age (AMA) and those affected by recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or severe male factor infertility (SMF). PGT-A was associated with significant improvements in the implantation rate (IR) and the ongoing pregnancy rate/live birth rate (OPR/LBR) per embryo transfer cycle in the AMA (39.3% vs. 16.2% [p<0.001] and 42.0% vs. 21.8% [p<0.001], respectively), RIF (41.7% vs. 22.0% [p<0.001] and 47.0% vs. 28.6% [p<0.001], respectively), and RPL (45.6% vs. 19.5% [p<0.001] and 49.1% vs. 24.2% [p<0.001], respectively) groups, as well as the IR in the SMF group (43.3% vs. 26.5%, p=0.011). Additionally, PGT-A was associated with lower overall incidence rates of early pregnancy loss in the AMA (16.7% vs. 34.3%, p=0.001) and RPL (16.7% vs. 50.0%, p<0.001) groups. However, the OPR/LBR per total cycle across all PGT-A groups did not significantly exceed that for the non-PGT-A groups. PGT-A demonstrated beneficial effects in high-risk patients. However, our findings indicate that these benefits are more pronounced in carefully selected candidates than in the entire high-risk patient population.

Evaluation of a long-acting recombinant bovine FSH for multiple ovulation and embryo transfer in dromedary camels

The present study was conducted to test a new super-agonist recombinant bovine FSH (rbFSH) to induce superovulation (SOV) in dromedary camels. In experiment I, a single IM injection of 40, 60, 80, 100, or 120 µg rbFSH was administered (4 donors per group) to determine the effective dose resulting in acceptable multiple ovulation and embryo yield. Administration of 40 µg was ineffective, while 100 and 120 µg were associated with increased numbers of developed follicles, corpora lutea, and recovered embryos compared to administration of 60 and 80 µg. In experiment II, donors were divided into treatment groups to compare rbFSH with two conventional protocols for SOV. Donors received a single dose of 2000 IU eCG in combination with 400 mg porcine follicle-stimulating hormone (pFSH; Folltropin-V®; Group 1, n = 29) or 500 µg of pFSH with 100 µg of pLH (Stimufol®; Group 2, n = 16). Group 3 (n = 19) received a single dose of 100 µg rbFSH. No difference was found in the size and number of follicles per donor. Response time, ovulation rate, and the number of corpora lutea and recovered embryos per donor were similar in all groups. The number of medium-sized and transparent embryos decreased while the number of small-sized and semi-transparent embryos increased in Group 3 (rbFSH) compared to the other two groups. The pregnancy rate of the recipients at 10 days post-ET, at two months of gestation, and the rate of early pregnancy loss (EPL) did not differ among the groups. In conclusion, a single IM administration of 100 µg rbFSH induces a successful superovulation in dromedary camels and has the advantage of reducing stress associated with multiple FSH administration of the conventional protocols.

#113 : Transdermal Oestrogen (GEL) for Endometrial Preparation in Frozen-Thawed Embryo Transfer

Background and Aims: Frozen-thawed embryo transfer (FET) requires a synchronization between endometrium and embryo. Pregnancy and live birth rates are proven to be significantly higher with FET due to better endometrial receptivity. In this study, we look at effectiveness oftwo oestrogen preparations in hormone replacement therapy (HRT) FET cycle on the pregnancy outcomes. Method: This is a retrospective analysis of 200 HRT FET cycles from 1st Jan 2020-31st December 2021, divided into 2 groups. Group 1 (n=100) received T Progynova 6 mg/day and Group 2 (n=100) received Oestrogel 6 mg/day (17B oestradiol 0.06% gel Besins France) starting on day 1 of menses, without GnRH agonist pituitary downregulation. The oestrogen dose was adjusted accordingly to achieve endometrial thickness (ET) of minimum 8 mm, prior to initiation of vaginal progesterone. The pregnancy outcomes (biochemical pregnancy, clinical pregnancy, ongoing pregnancy, early pregnancy loss and ectopic pregnancy rates), duration of oestrogen usage and endometrial thickness measurement prior to embryo transfer were analysed. Results: The biochemical pregnancy rate in this study was 39%, with a clinical pregnancy rate of 31%. Comparing both preparations, the biochemical pregnancy rate (p=0.562), clinical pregnancy rate (p=0.705), ongoing pregnancy rate (p=0.623), and early pregnancy loss rate (p=0.705) were not statistically significant. The duration required to achieve optimal endometrial thickness (p=0.212), and endometrial thickness measurement prior to vaginal progesterone commencement (p=0.335) were comparable. Conclusion: Oestrogel is a non-inferior option to oestradiol valerate for endometrial preparation in HRT FET cycles, especially for patients with high risk of venous thromboembolism due to its safety profile.

Preconception Non-criteria Antiphospholipid Antibodies and Risk of Subsequent Early Pregnancy Loss: a Retrospective Study

The aim of this study was to investigate the subsequent early pregnancy outcomes in women positive for non-criteria antiphospholipid antibodies (NC-aPLs) before pregnancy. A total of 273 patients who had experienced sporadic or recurrent pregnancy loss and had been screened for 13 NC-aPLs at preconception were recruited in this study from September 2019 to February 2022. Serum levels of NC-aPLs were measured by ELISA using specific kits. The primary outcome was early pregnancy loss, and the secondary outcomes were biochemical pregnancy, clinically confirmed pregnancy loss, and ongoing pregnancy. Among these subjects, 56 patients had one previous pregnancy loss, and 217 had recurrent pregnancy loss (RPL). The NC-aPLs (+) and NC-aPLs (−) groups had similar rates of early pregnancy loss (EPL) after adjustment, regardless of the number of positive NC-aPLs (aOR = 1.054, 95% CI 0.602–1.846). Other outcomes were comparable in both groups, including the rates of biochemical pregnancy (aOR = 1.344, 95% CI 0.427–4.236), clinically confirmed pregnancy loss (aOR = 0.744, 95% CI 0.236–2.344), and ongoing pregnancy (aOR = 0.949, 95% CI 0.542–1.660). Based on sensitivity analysis, the NC-aPLs (+) were not associated with adverse early pregnancy outcomes in women with RPL. Furthermore, the difference in gestational weeks of pregnancy loss between the two groups was also insignificant. This study found no evidence linking preconception NC-aPL positivity to early pregnancy outcomes but offers a reference for future research to clarify NC-aPLs’ potential clinical impact.

Antibiotic cured chronic endometritis remains a risk factor for early pregnancy loss in the subsequent frozen euploid embryo transfer

Research questionDo patients with antibiotic-cured chronic endometritis (CCE) have a comparable pregnancy outcome to those with non-chronic endometritis (NCE) in the subsequent frozen embryo transfer (FET) cycle? DesignA retrospective cohort analysis included 833 patients in their first FET cycles with single euploid embryo transfer. Chronic endometritis (≥5 CD138+ plasma cells per high-power field [CD138+/HPF]) was treated with standard antibiotic therapy. Patients were classified into two groups: the NCE group (n = 611, <5 CD138+/HPF) and the CCE group (n = 222, ≥5 CD138+/HPF and cured after antibiotic treatment). Pregnancy outcomes were compared. NCE group was divided into subgroup 1 (CD138+/HPF = 0) and subgroup 2 (CD138+/HPF = 1–4) for further analysis. ResultsThe rate of early pregnancy loss (EPL), incorporating all losses before 10 weeks’ gestation, was significantly higher in the CCE group than the NCE group (21.2% versus 14.2%, P = 0.016), and the difference was statistically significant (adjusted odds ratio [AOR] 1.68, 95% confidence interval [CI] 1.11–2.55). No significant differences were observed between the two groups with regard to other pregnancy outcomes. In the subgroup analysis, the EPL rate and biochemical pregnancy rate were significantly higher in subgroup 2 than subgroup 1 (17.2% versus 9.4%, AOR 2.21, 95% CI 1.30–3.74; 12.2% versus 6.9%, AOR 2.01, 95% CI 1.09–3.68). ConclusionsChronic endometritis cured by standard antibiotic therapy remains a risk factor for EPL in FET cycles, although no differences were found in live birth rates between patients with CCE or with NCE.

Impacts of the COVID-19 pandemic on early pregnancy outcomes among women undergoing frozen-thawed embryo transfer: a retrospective cohort study

The effect of COVID-19 pandemic on early pregnancy outcomes among women undergoing frozen-thawed embryo transfer (FET) remains unclear. We aimed to evaluate whether early pregnancy outcomes were altered in patients undergoing FET during the pandemic. In this retrospective cohort study, women conceived through FET in 2016–2021 from two hospitals in China were included. The early pregnancy outcomes were compared using Logistic regression model, including biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), and early pregnancy loss rate (EPLR). A total of 16,669 (67.2%) and 6,113 (26.8%) FET cycles enrolled before and during the pandemic, respectively. Univariate analyses showed that women undergoing FET during the pandemic had significantly increased BPR (72.9% vs. 69.7%) and CPR (59.5% vs. 55.0%), and significantly decreased EPLR (13.7% vs. 16.7%) compared to pre-pandemic (all P < 0.001). Moreover, after adjustment, the results were in accordance with univariate analysis for CPR [adjusted OR (95%CI) = 1.08 (1.01–1.14)] and EPLR [adjusted OR (95%CI) = 0.82 (0.73–0.91)], while the statistical significance between BPR and the pandemic disappeared. In summary, women conceived by FET did not have a reduced possibility of clinical pregnancy and a higher risk of early pregnancy loss during the pandemic compared with the pre-pandemic.

Finding of the optimal preparation and timing of endometrium in frozen-thawed embryo transfer: a literature review of clinical evidence.

Frozen-thawed embryo transfer (FET) has been a viable alternative to fresh embryo transfer in recent years because of the improvement in vitrification methods. Laboratory-based studies indicate that complex molecular and morphological changes in endometrium during the window of implantation after exogenous hormones with controlled ovarian stimulation may alter the interaction between the embryo and endometrium, leading to a decreased implantation potential. Based on the results obtained from randomized controlled studies, increased pregnancy rates and better perinatal outcomes have been reported following FET. Compared to fresh embryo transfer, fewer preterm deliveries, and reduced incidence of ovarian hyperstimulation syndrome were found after FETs, yet there is a trend of increased pregnancy-related hypertensive diseases in women receiving FET. Despite the increased application of FET, the search for the most optimal priming protocol for the endometrium is still undergoing. Three available FET protocols have been proposed to prepare the endometrium: i) natural cycle (true natural cycle and modified natural cycle) ii) artificial cycle (AC) or hormone replacement treatment cycle iii) mild ovarian stimulation (mild-OS) cycle. Emerging evidence suggests that the optimal timing for FET using warmed blastocyst transfer is the LH surge+6 day, hCG administration+7 day, and the progesterone administration+6 day in the true natural cycle, modified natural cycle, and AC protocol, respectively. Although still controversial, better clinical pregnancy rates and live birth rates have been reported using the natural cycle (true natural cycle/modified natural cycle) compared with the AC protocol. Additionally, a higher early pregnancy loss rate and an increased incidence of gestational hypertension have been found in FETs using the AC protocol because of the lack of a corpus luteum. Although the common clinical practice is to employ luteal phase support (LPS) in natural cycles and mild-OS cycles for FET, the requirement for LPS in these protocols remains equivocal. Recent findings obtained from RCTs do not support the routine application of endometrial receptivity testing to optimize the timing of FET. More RCTs with rigorous methodology are needed to compare different protocols to prime the endometrium for FET, focusing not only on live birth rate, but also on maternal, obstetrical, and neonatal outcomes.

Metabolomic evolution of the postpartum dairy cow uterus.

High rates of early pregnancy loss are a critical issue in dairy herds, particularly in seasonal, grazing systems. Components of the uterine luminal fluid (ULF), on which the early embryo depends for sustenance and growth, partly determine early pregnancy losses. Here, changes in ULF from early to mid-postpartum in crossbred dairy cows were explored, linking them with divergent embryo development. For this, the uteri of 87 cows at Day 7 of pregnancy at first and third estrus postpartum were flushed to collect ULF. Eighteen metabolites (chiefly organic acids and sugars) significantly varied in abundance across postpartum, indicating a molecular signature of physiological recovery consistent of the upregulation of pyrimidine metabolism and glycerophospholipid metabolism, and downregulation of pentose phosphate and taurine metabolism pathways. Joint pathway analysis of metabolomics data and a previously generated proteomics data set on the same ULF samples suggests key links between postpartum recovery and subsequent successful embryo development. These include upregulation of VEGFA and downregulation of metabolism, NRF2, T-cell receptor, which appear to improve the ULF's capacity of sustaining normal embryo development, and a putative osmo-protectant role of beta-alanine. These relationships should be further investigated to develop tools to detect and reduce early pregnancy loss in dairy cows.