From Comprehensive Evaluation to Early Pregnancy Outcome Associated Factors in Women with Recurrent Pregnancy Loss

Authors: Asrin Ainsworth; T. Göggl; T. Strowitzki; B. Toth; R.J. Kuon

Recurrent pregnancy loss (RPL), affecting approximately 1–3% of couples, is associated with multiple clinical, anatomical, endocrine, genetic, and immunological factors. However, the underlying cause remains unexplained in many cases, and reliable predictors of future pregnancy outcomes are limited. This retrospective study evaluated clinical and immunological factors associated with first-trimester pregnancy outcomes in women with RPL after standardized diagnostic evaluation and management.

The single-center study included 891 women with RPL evaluated at a tertiary university referral center between November 2011 and March 2019. Women with a history of two or more pregnancy losses underwent standardized assessment, including reproductive history, uterine anatomy evaluation, endocrine testing, thrombophilia screening, parental karyotyping, autoimmune testing, and endometrial biopsy assessment for uterine natural killer (uNK) cells and plasma cells. Identified abnormalities were managed according to local clinical practice. Subsequent pregnancy outcomes beyond 12 weeks of gestation were available for 327 index pregnancies.Among the 327 women with a subsequent pregnancy, 208 (64%) achieved an ongoing pregnancy beyond 12 weeks of gestation, while 119 (36%) experienced another pregnancy loss. Women with ongoing pregnancies had fewer previous pregnancy losses compared with those who experienced a subsequent loss (2.94 ± 0.82 vs. 3.33 ± 1.19; p = 0.0006). Maternal age was similar between women with pregnancy loss and those with ongoing pregnancies (35.53 ± 4.07 years vs. 36.10 ± 4.31 years; p = 0.25).Submucous fibroids were identified more frequently in women whose pregnancies ended in loss compared with those with ongoing pregnancies (11.97% vs. 3.92%; p = 0.006). At the first pregnancy presentation, levels of early pregnancy hormones, including beta-human chorionic gonadotropin (β-hCG), progesterone, and estradiol, were significantly higher in women with ongoing pregnancies (all p < 0.05).No significant differences in pregnancy outcomes were observed for other evaluated parameters, including uterine factors, endocrine findings, thrombophilia markers, parental genetic findings, autoimmune factors, or endometrial immune parameters after standardized evaluation and management. Progesterone supplementation and L-thyroxine therapy were used more frequently in pregnancies that continued beyond 12 weeks.

The study had limitations due to its retrospective, single-center design, which may affect the ability to establish causal relationships and the generalizability of findings. Additionally, management of identified abnormalities during clinical care may have influenced pregnancy outcomes and limited assessment of the independent predictive value of individual diagnostic factors.

In conclusion, among women with recurrent pregnancy loss, subsequent first-trimester pregnancy outcomes were associated with the number of previous losses, presence of submucous fibroids, and early pregnancy hormone levels, while standardized evaluation findings related to immunological, genetic, endocrine, and thrombophilic factors were not associated with outcomes.

Analysis of Structural Variants Identified by Optical Genome Mapping in Patients with Recurrent Implantation Failure and Recurrent Pregnancy Loss

Authors: Francisca María Lozano; B. Lledó; R. Morales; J.A. Ortiz; A. Fuentes; A. Bernabeu

Chromosomal structural variants (SVs) are recognized genetic contributors to infertility, recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), and congenital abnormalities. Conventional cytogenetic methods such as karyotyping may not detect small or cryptic chromosomal rearrangements due to limited resolution. This prospective clinical trial evaluated whether Optical Genome Mapping (OGM), a high-resolution genomic technology, could identify previously undetected structural variants associated with infertility in couples with RIF and RPL.

The prospective, non-randomized cohort study included 395 patients comprising 186 couples and 23 single female patients undergoing assisted reproductive technology (ART) between March 2023 and July 2025. Among the participants, 51% had RIF and 49% had RPL. All participants had normal results on conventional G-banded karyotyping. OGM was performed as a high-resolution diagnostic approach to identify cryptic chromosomal structural variants potentially associated with infertility. Genomic DNA was isolated from frozen peripheral blood samples, and OGM analysis was performed using the Saphyr platform. Structural variants were identified by comparing genome maps with the reference genome GRCh38/hg38. The mean age of female and male participants was 37.3 ± 3.7 years and 39.7 ± 5.6 years, respectively, with an average infertility duration of 3.8 ± 1.9 years. Clinical characteristics were comparable between the RPL and RIF groups. As expected, women with RPL had a higher number of previous miscarriages compared with women with RIF (3.6 vs. 0.7; p < 0.001), while patients with RIF underwent more embryo transfers compared with those with RPL (2.7 vs. 5.3; p < 0.001). OGM identified 32 structural variants among 395 individuals with previously normal karyotypes, resulting in an overall diagnostic yield of 8.1%. The detected variants included 19 small inversions (4.8%), 7 large inversions (1.7%), 4 translocations (1.0%), and 2 interchromosomal insertions (0.5%). Additionally, 104 small insertions and deletions were detected in genes associated with reproductive function. The frequency of OGM-detected alterations was similar between the RIF and RPL groups (p = 0.418). Further analysis showed differences in semen quality between men with and without OGM-detected alterations (45.9% vs. 67.5%; p = 0.011). Couples with OGM alterations also had higher embryo aneuploidy rates compared with those without alterations (57.9% vs. 45.3%; p = 0.049). However, clinical reproductive outcomes were similar, which may be related to embryo selection using preimplantation genetic testing for aneuploidy (PGT-A).

The study was limited by its single-center design, lack of functional validation of detected variants, uncertainty in the clinical significance of some structural variants, and the small number of pathogenic findings. The use of PGT-A may also have reduced observable differences in reproductive outcomes.

In conclusion, Optical Genome Mapping identified cryptic structural variants in patients with recurrent implantation failure and recurrent pregnancy loss despite normal conventional karyotyping, suggesting that OGM may improve genetic evaluation of infertility by detecting chromosomal alterations missed by standard cytogenetic methods.

Atosiban Improves Implantation Rates in Patients with Elevated Uterine Contractility: A Counterfactual Analysis at Different UC Thresholds

Authors: Belen Moliner; L.S. Gorgan; A. Herencia Rivero; G. Bertapelle; C. Quetglas Muñoz; V. Legidos Lopez; A. Bernabeu García

Elevated uterine contractility (UC) during embryo transfer may negatively affect implantation by interfering with endometrial receptivity and embryo positioning. Although atosiban, an oxytocin receptor antagonist, has been investigated for reducing uterine contractions and improving assisted reproductive technology (ART) outcomes, the optimal UC threshold for initiating treatment and the extent of benefit according to UC severity remain unclear. This retrospective cohort study evaluated the effect of atosiban on reproductive outcomes across different UC thresholds using a counterfactual analysis approach.

The study included patients undergoing embryo transfer at Instituto Bernabeu, Alicante, Spain. Data were analyzed from a pre-treatment period (2015–2016; n = 83 with measured UC), during which atosiban was not routinely used, and a post-treatment period (2017–2025; n = 795), during which atosiban was administered to patients with UC ≥1.5. Three UC thresholds were evaluated: UC ≥1.5 (270 treated patients), UC ≥2.0 (122 treated patients), and UC ≥2.5 (34 treated patients). Atosiban was administered as a bolus on the day of embryo transfer when elevated UC was detected by transvaginal ultrasound. The primary outcome was beta-human chorionic gonadotropin (β-hCG) positivity, while secondary outcomes included ongoing pregnancy and live birth. Treatment effects were estimated using a three-step counterfactual analysis that assessed the effect of UC on outcomes without treatment, compared treated and untreated groups, and calculated the estimated benefit of atosiban. In the pre-treatment period, higher UC levels were associated with lower β-hCG positivity rates. UC ≥1.5 was associated with a 27.2 percentage point reduction in β-hCG positivity (78.8% vs. 51.6%; p = 0.020), while UC ≥2.0 showed a 41.3 percentage point reduction (74.6% vs. 33.3%; p = 0.007). For UC ≥2.5, the reduction was 36.7 percentage points, although this was not statistically significant (70.0% vs. 33.3%; p = 0.196).

Among patients with UC ≥1.5, those treated with atosiban had higher β-hCG positivity compared with controls (53.8% vs. 43.5%; p = 0.009). The estimated treatment effect was +37.6 percentage points, with a number needed to treat (NNT) of 2.7. Live birth rates were 28.1% with atosiban and 25.1% in controls, with an estimated treatment effect of +18.8 percentage points (NNT = 5.3). For patients with UC ≥2.0, atosiban treatment resulted in higher β-hCG positivity compared with controls (56.7% vs. 45.2%; p = 0.030). The estimated treatment effect was +52.8 percentage points, corresponding to an NNT of 1.9. Live birth rates were 30.9% with atosiban compared with 25.3% in controls, with an estimated effect of +33.3 percentage points (NNT = 3.0). Among patients with the highest UC level (UC ≥2.5), β-hCG positivity was 63.0% with atosiban compared with 46.3% in controls (p = 0.088), with an estimated treatment effect of +53.4 percentage points and an NNT of 1.9. Live birth rates were significantly higher with atosiban (44.4% vs. 25.3%; p = 0.026), with an estimated treatment effect of +41.6 percentage points and an NNT of 2.4. The treatment benefit increased progressively with higher UC thresholds, showing a dose-response relationship. The study was limited by its non-randomized design, potential confounding by indication, limited sample size in higher UC groups, and the need for randomized controlled trials to confirm causal effects.

In conclusion, atosiban was associated with improved reproductive outcomes in patients with elevated uterine contractility during embryo transfer, with UC ≥2.0 identified as the threshold providing the best balance between clinical benefit and patient coverage, while UC ≥2.5 showed the greatest benefit among patients with higher UC levels.

Pre-Conception and First Trimester Metformin on Miscarriage Risk in Women with Polycystic Ovary Syndrome: A Randomised, Placebo-Controlled Trial

Authors: Adam Devall; R. Smith; L. Priest; G. Mitchell; P. Nnamani; V. Cheed; L. Middleton; K. Vigneswaran; P. Melo; A. Coomarasamy

Polycystic ovary syndrome is associated with an increased risk of miscarriage, and metformin is commonly used before conception to improve ovulation and metabolic health. However, evidence on whether continuing metformin during the first trimester reduces miscarriage risk remains inconsistent, and its routine use during early pregnancy is still debated.

This multicenter, double-blind, randomized, placebo-controlled trial evaluated whether starting metformin before conception and continuing it through the first trimester reduces the risk of miscarriage in women with polycystic ovary syndrome (PCOS). The study was a pre-specified miscarriage prevention analysis nested within the LOCI 2×2 factorial trial, which compared letrozole and clomifene, with or without metformin, for ovulation induction in women with PCOS. Women aged 18–42 years with anovulatory PCOS, diagnosed using the Rotterdam criteria, were recruited from 48 hospitals across the United Kingdom. Participants were randomized to receive oral metformin (500–1500 mg daily) or matched placebo before conception. Women who became pregnant continued treatment until 14 weeks of gestation. The primary outcome was miscarriage before 24 weeks of pregnancy. A total of 1,739 women were randomized between November 2020 and February 2024. The primary analysis will compare miscarriage rates before 24 weeks between the metformin and placebo groups. Adjusted risk estimates, 95% confidence intervals, and p values will be reported using Poisson regression models. Secondary outcomes will include ongoing pregnancy at 12 weeks, live birth after 24 weeks, multiple pregnancy, ectopic pregnancy, stillbirth, and termination of pregnancy. Prespecified subgroup analyses based on maternal age, body mass index, and previous pregnancy history will also be presented. Maternal and neonatal serious adverse events and congenital abnormalities will be evaluated to assess the safety of metformin. The study may not have sufficient power to detect differences in rare outcomes such as stillbirth. In addition, treatment was stopped at 14 weeks of gestation, so the effects of continuing metformin beyond the first trimester remain unknown.

Overall, the trial is designed to determine whether preconception metformin continued through the first trimester reduces miscarriage risk in women with PCOS. The efficacy and safety results will be presented at the conference.

Impact of Pre-Transfer Serum Progesterone Fluctuation on Implantation in Single Euploid Hormonal-Replacement-Therapy Frozen Embryo Transfer (HRT-FET) Cycles.

Authors: Suzan Samir; H. Didar; B. Lawrenz; R. Del Gallego; S. Selim; H. Fatemi

Hormonal replacement therapy is widely used for endometrial preparation in frozen embryo transfer cycles, and adequate progesterone exposure is essential for successful implantation. While low serum progesterone levels before embryo transfer have been linked to poorer outcomes, the impact of fluctuations in progesterone levels before transfer, particularly in single euploid embryo transfer cycles, remains uncertain.

This retrospective cohort study evaluated whether short-term changes in serum progesterone (P4) levels before embryo transfer affect implantation in single euploid hormonal replacement therapy frozen embryo transfer (HRT-FET) cycles. The study included 231 single euploid HRT-FET cycles performed between January 2023 and December 2025. Serum progesterone levels were measured one day before embryo transfer (ET−1) and again on the day of embryo transfer. Patients received oral estradiol valerate for endometrial preparation, followed by exogenous progesterone once a triple-line endometrium was achieved. Embryo transfer was performed five days after progesterone initiation. Progesterone fluctuation was defined as the absolute change in serum progesterone (|ΔP4|). Implantation was defined by serum beta-human chorionic gonadotropin (β-hCG) levels of at least 15 mIU/mL. Multivariable logistic regression adjusted for age, body mass index (BMI), and embryo quality. The median progesterone fluctuation was 3.63 ng/mL, dividing patients into low-fluctuation (≤3.63 ng/mL; n=116) and high-fluctuation (>3.63 ng/mL; n=115) groups. Baseline age, BMI, and embryo quality were similar between the groups (all p>0.25). As expected, progesterone levels on embryo transfer day were higher in the high-fluctuation group than in the low-fluctuation group (17.32 vs. 11.33 ng/mL; p<0.001), with significantly greater absolute progesterone changes (8.65 vs. 1.54 ng/mL; p<0.001). Implantation occurred in 71.6% of the low-fluctuation group and 67.0% of the high-fluctuation group. After adjustment for age, BMI, and embryo quality, high progesterone fluctuation was not associated with implantation (adjusted odds ratio [aOR] 0.78; 95% confidence interval [CI] 0.44–1.38; p=0.395). Similarly, when progesterone fluctuation was analyzed as a continuous variable, no association with implantation was observed (aOR 1.006 per 1 ng/mL increase; p=0.758). The retrospective design, relatively small sample size, and variation in luteal phase support regimens, progesterone administration, and blood sampling times may have influenced the results.

Overall, short-term fluctuations in serum progesterone before embryo transfer were not associated with implantation in single euploid HRT-FET cycles.

Letrozole Versus Hormone Replacement Therapy for Frozen Embryo Transfer in Women with PCOS: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs)

Authors: Sezcan Mumusoglu; M. Erden; S.B. Telek; H. Yarali

Hormonal replacement therapy and letrozole-stimulated protocols are both used for endometrial preparation in frozen embryo transfer cycles for women with polycystic ovary syndrome. However, it remains uncertain whether letrozole provides better reproductive or perinatal outcomes than hormone replacement therapy.

This systematic review and meta-analysis evaluated whether letrozole-stimulated endometrial preparation improves reproductive and perinatal outcomes compared with hormone replacement therapy (HRT) in frozen embryo transfer (FET) cycles among women with polycystic ovary syndrome (PCOS). The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched Medical Literature Analysis and Retrieval System Online(MEDLINE), Excerpta Medica Database (Embase), Global Health, and the Cochrane Library through September 10, 2025. Only randomized controlled trials (RCTs) comparing letrozole-stimulated and HRT protocols in women with PCOS undergoing FET were included. Outcomes were pooled using random-effects models. Risk of bias was assessed with RoB-2, and the certainty of evidence was evaluated using GRADE. Four RCTs involving 891 women were included, with 448 women in the letrozole group and 443 in the HRT group. Live birth rates were similar between the two protocols (risk ratio [RR] 0.92; 95% confidence interval [CI] 0.79–1.07; I²=2.2%). Clinical pregnancy rates also did not differ significantly (RR 0.95; 95% CI 0.81–1.12; I²=38.8%), nor did miscarriage rates (RR 1.24; 95% CI 0.83–1.84; I²=0%). There was no significant difference in hypertensive disorders of pregnancy between the two groups (RR 2.81; 95% CI 0.83–9.50; I²=0%), although the pooled prevalence was numerically lower with letrozole (2.4%) than with HRT (5.5%). Gestational diabetes mellitus occurred less frequently in the HRT group (RR 0.33; 95% CI 0.14–0.82). No significant differences were observed in preterm birth, macrosomia, low birth weight, or cycle cancellation before FET. Three of the four included trials had a low risk of bias, while one study had some concerns. The findings may have limited generalizability because most studies were conducted in China and were single-center trials. In addition, the sample sizes were insufficient to draw firm conclusions about perinatal outcomes.

Overall, evidence from randomized controlled trials showed that letrozole-stimulated and hormone replacement therapy protocols provide comparable live birth and pregnancy outcomes in women with PCOS undergoing frozen embryo transfer.

The Effect of Intrauterine Platelet-Rich Plasma Infusion on Clinical Pregnancy Outcomes in Patients with Recurrent Implantation Failure

Authors: Ying Huang; R. Yang; S. Yang; Y. Wang; R. Li

Intrauterine platelet-rich plasma has been proposed as a treatment to improve embryo implantation and pregnancy outcomes in women with recurrent implantation failure. However, evidence regarding its effectiveness remains inconclusive, and it is unclear which patient groups benefit the most.

This prospective cohort study evaluated whether intrauterine platelet-rich plasma (PRP) infusion improves outcomes in frozen embryo transfer (FET) cycles among patients with recurrent implantation failure (RIF) and identified the patient groups most likely to benefit. The study analyzed 1,846 FET cycles performed between July 2023 and March 2025 in women younger than 40 years with a history of three or more previous implantation failures. Of these, 571 cycles received PRP infusion and 1,275 cycles served as controls. Multivariable logistic regression was used to adjust for potential confounding factors. The clinical pregnancy rate (CPR) was significantly higher in the PRP group than in the control group (41.0% vs. 36.2%; p=0.048). After adjustment for confounding factors, PRP infusion remained independently associated with a higher CPR (adjusted odds ratio [OR] 1.291; 95% confidence interval [CI] 1.034–1.613). Subgroup analyses showed that the benefit of PRP was greatest in older women, with CPR increasing from 32.7% in the control group to 41.3% in the PRP group (adjusted OR 1.554; 95% CI 1.156–2.091). Women who did not undergo preimplantation genetic testing (PGT) also had significantly higher CPR with PRP (39.9% vs. 32.2%; adjusted OR 1.260; 95% CI 1.005–1.579). No significant differences were observed in other subgroups, including those based on the number of previous embryo transfer failures, infertility type, FET protocol, or embryo stage transferred. Among patients who received PRP, the clinical pregnancy rate showed a declining trend with longer PRP cryopreservation time. Although the CPR decreased to 13.3% when PRP was cryopreserved for more than three months, the difference was not statistically significant. As a single-center prospective cohort study, residual confounding cannot be completely excluded, and the findings may not be generalizable. The biological mechanisms underlying the greater benefit in specific patient subgroups also require further investigation.

Overall, the study suggests that intrauterine PRP infusion improves clinical pregnancy rates in women with recurrent implantation failure undergoing FET, with the greatest benefit seen in older women and those who do not undergo preimplantation genetic testing.

A Real World Evidence Generation in Luteal Phase Support with Dydrogesterone for Impact on Safety & Reproductive Outcomes

Authors: Rohan Palshetkar; N. Palshetkar; P. Tank; A. Purandare

Luteal phase support is an essential component of assisted reproductive technology, and progesterone can be administered through several routes. Previous clinical trials have shown that oral dydrogesterone has similar efficacy and safety to vaginal progesterone for fresh and frozen embryo transfer cycles, while offering the convenience of oral administration.

This prospective, observational, multicenter study evaluated the reproductive outcomes and safety of oral dydrogesterone for luteal phase support (LPS) in women undergoing assisted reproductive technology (ART). The study was conducted between December 2023 and June 2025 and included 768 women aged 21 years and older who underwent embryo transfer. Patients received dydrogesterone for LPS and were followed after embryo transfer. The primary outcome was the detection of fetal heartbeat (FHB), along with overall assessments by physicians and patients. Secondary outcomes included pregnancy rates, vaginal bleeding, and safety. The participants had a mean age of 33.32 ± 5.06 years, a mean body weight of 62.83 ± 10.48 kg, and a mean body mass index (BMI) of 24.49 ± 3.78 kg/m². Biochemical pregnancy was confirmed in 605 patients (78.8%) at 12 days after embryo transfer. Clinical pregnancy, confirmed by the presence of a fetal heartbeat, was achieved in 521 patients (67.8%) at 30 days after embryo transfer. The ongoing pregnancy rate (OPR), confirmed by a positive fetal heartbeat at 70 days, was 66.8% (513 patients). Dydrogesterone was reported to be an effective and easy-to-use option for luteal phase support, with only a few minor side effects observed during the study. The lack of a control or comparator group limits the ability to directly attribute the observed outcomes to dydrogesterone alone.

Overall, the study suggests that oral dydrogesterone is associated with high clinical pregnancy and ongoing pregnancy rates in women undergoing assisted reproductive technology and may offer a convenient option for luteal phase support.

A Real-World Comparative Effectiveness Analysis of Assisted Reproduction Strategies in Recurrent Pregnancy Loss: A 12-year Single-Centre Experience

Authors: Gobbilla Tejaswini; D.R. Gedela; K.C. Mantravadi

Recurrent pregnancy loss (RPL) has multiple possible causes, including genetic, endocrine, immunological, and anatomical factors, although many cases remain unexplained. Current European Society of Human Reproduction and Embryology (ESHRE) guidelines recommend thorough evaluation and management of modifiable risk factors, while advising caution with additional therapies because evidence for their benefit is limited. However, assisted reproduction and adjunctive treatments are often used in clinical practice, and comparative data on their outcomes remain limited.

This retrospective real-world study evaluated whether commonly used assisted reproduction strategies improve pregnancy outcomes in women with recurrent pregnancy loss compared with standard supportive care. The analysis included data from 300 couples with a history of two or more pregnancy losses who were treated at a single fertility center between January 2012 and December 2024. Women with identified endocrine, metabolic, or immunological abnormalities received standard treatment before or alongside assisted reproduction. The management strategies included standard supportive care with non-preimplantation genetic testing embryo transfer and antithrombotic support (n=22), euploid embryo transfer following preimplantation genetic testing for aneuploidy (n=142), peripheral blood mononuclear cell therapy (n=49), and intravenous immunoglobulin therapy (n=50). The primary outcomes were clinical pregnancy rate, miscarriage rate, and live birth rate.

Most women were 30–35 years old (44%), followed by those aged 25–30 years (31%). Overweight or obesity was present in 73.6% of women, and 88.7% had primary recurrent pregnancy loss. Endocrine abnormalities were the most common underlying factor (56%), followed by immunological (17%) and anatomical abnormalities (9%). Confirmed genetic abnormalities were identified in only a minority of patients because genetic testing was incomplete.Miscarriage occurred across all treatment groups, with rates comparable to those reported in unselected assisted reproduction populations. Women who underwent euploid embryo transfer had a miscarriage rate of 15% and a live birth rate of 71.8%. In the peripheral blood mononuclear cell group, the miscarriage rate was 18.6% and the live birth rate was 63.2%. Women treated with intravenous immunoglobulin had a miscarriage rate of 27% and a live birth rate of 72%. Those managed with standard supportive care alone had a miscarriage rate of 20% and a live birth rate of 55%.Among the evaluated strategies, euploid embryo transfer was associated with the lowest miscarriage proportion. However, because this was an observational study, the findings do not support or refute the routine use of adjunctive therapies, and no causal relationship can be established. The study was limited by its retrospective, non-randomized design, small subgroup sizes, incomplete genetic testing, lack of systematic evaluation of male factors, and inclusion of patients from a single ethnic population.

Overall, miscarriage remained a persistent outcome despite different management strategies. The findings support guideline-based evaluation, transparent patient counselling, and shared decision-making, while highlighting the need for prospective studies to identify patients who may benefit most from genetic selection strategies.

Serum Progesterone and Estradiol Levels on the First Pregnancy Test Day as Predictors of Live Birth After Fresh Embryo Transfer

Authors: Tesniem Aouragh; C. Roelens; N. Ranisavljevic; L. Van Landuyt; M. De Vos; H. Tournaye; C. Blockeel; S. Mackens

Luteal phase support is an essential part of fresh embryo transfer (ET) cycles because ovarian stimulation can reduce natural luteinizing hormone secretion and lead to luteal phase insufficiency. Although optimal progesterone levels during the early and mid-luteal phase have been suggested, the ideal estradiol levels and the value of measuring these hormones on the pregnancy test day remain unclear.

This retrospective single-center cohort study evaluated whether serum progesterone and estradiol levels measured on the first pregnancy test day could predict the likelihood of live birth after fresh embryo transfer. The study analyzed 771 fresh blastocyst transfer cycles performed between November 2020 and March 2024 in women with a positive serum human chorionic gonadotropin (hCG) test (>10 IU/L) and a body mass index below 35 kg/m². Hormone levels were measured 9–12 days after embryo transfer, and a multivariable model was developed to estimate the probability of live birth. The mean maternal age was 34.10 ± 4.34 years, and the mean body mass index was 24.35 ± 4.52 kg/m². The mean serum progesterone level on the pregnancy test day was 44.66 ± 19.60 µg/L, while the mean estradiol level was 806.51 ± 712.41 ng/L.

Higher progesterone levels were associated with a greater likelihood of live birth (odds ratio 1.054 per µg/L; 95% confidence interval 1.040–1.068; p<0.001). Higher estradiol levels were also associated with increased odds of live birth (odds ratio 1.003 per ng/L; 95% confidence interval 1.001–1.005; p=0.009). A significant interaction between progesterone and estradiol (p=0.006) suggested that the effects of the two hormones were interdependent. Live birth rates increased with rising progesterone and estradiol levels before reaching a plateau at approximately 25 µg/L for progesterone and 700 ng/L for estradiol.

Increasing maternal age was associated with lower odds of live birth (odds ratio 0.911 per year; 95% confidence interval 0.873–0.950; p<0.001), while cycles performed for male-factor infertility had higher odds of live birth (odds ratio 1.57; 95% confidence interval 1.06–2.32; p=0.024). The final prediction model showed acceptable performance, with an area under the curve of 0.745, explained 24% of the variation in outcomes (Nagelkerke R²=0.243), correctly classified 74.8% of cycles, and achieved balanced sensitivity and specificity of 69% using a probability threshold of 0.72.The study was limited by its retrospective, single-center design, which may have introduced selection bias and residual confounding. In addition, progesterone values above the assay detection limit were truncated, which may have affected estimates at higher concentrations.

Overall, serum progesterone and estradiol levels measured on the first pregnancy test day after fresh embryo transfer were associated with the probability of live birth, and a multivariable model was developed to estimate individualized live birth probability. Further studies are needed to determine whether adjusting progesterone or estradiol levels can improve live birth outcomes.

Randomized Control Study on The Safety and Efficacy of Triangular 3-Bites Cervical Cerclage Versus McDonald Technique in Improving Pregnancy Outcome in Cervical Insufficiency

Authors: Joseph Ikechebelu; B. Okpala; C. Dim; G. Eleje; N. Joe-Ikechebelu; L. Nwajiaku; I. Albert; P. Okam; C. Nwachukwu

Cervical insufficiency is an important cause of mid-trimester miscarriage and preterm birth, and cervical cerclage is the standard treatment. The McDonald technique is the most commonly used method but can be technically difficult in women with a short or small cervix and may be prone to slippage.

This study evaluated a new triangular 3-bites technique designed to simplify the procedure while maintaining similar effectiveness. This randomized controlled trial was conducted in two private multispecialty hospitals in Nigeria between February 2021 and January 2022. A total of 206 pregnant women requiring cervical cerclage based on their history or ultrasound findings were randomly assigned in a 1:1 ratio to undergo either the triangular 3-bites technique or the conventional McDonald technique. There were no significant differences in baseline characteristics between the groups. The mean gestational age at cerclage insertion was similar (14 weeks 6 days ± 2 weeks 1 day vs 15 weeks 0 days ± 2 weeks 5 days; p=0.57), as was the mean gestational age at delivery (36 weeks 5 days ± 2 weeks 6 days vs 36 weeks 4 days ± 2 weeks 2 days; p=0.77).

Pregnancy outcomes were comparable between the two techniques. Miscarriage rates were 10.7% with the triangular 3-bites technique and 12.6% with the McDonald technique (p=0.66). Preterm delivery occurred in 25.7% and 27.2% of women, respectively (p=0.63), while term delivery rates were 63.1% and 62.1% (p=0.88). The triangular 3-bites technique resulted in a significantly higher mean birth weight (2.82 ± 0.97 kg vs 2.54 ± 1.00 kg; p<0.01) and a shorter procedure time (4 minutes 40 seconds ± 2 minutes 12 seconds vs 7 minutes 25 seconds ± 2 minutes 57 seconds; p<0.01). The procedure was also reported to be easier to perform and was associated with lower estimated blood loss (22.96 ± 21.77 mL vs 26.89 ± 24.74 mL), although the difference in blood loss was not statistically significant (p=0.17). Unlike the McDonald group, the triangular 3-bites group showed no significant changes in uterine artery resistance index or systolic/diastolic ratio on Doppler velocimetry. As this was the first trial evaluating the triangular 3-bites technique and was conducted at only two centers, additional randomized controlled trials in different settings and long-term follow-up are needed before the findings can be generalized.

Overall, the triangular 3-bites technique was non-inferior to the McDonald technique in terms of pregnancy outcomes and offered the advantages of easier application, shorter procedure time, and lower blood loss, making it an effective alternative for cervical cerclage.

Intragestational Methotrexate for Caesarean Scar Pregnancy: High Response Rates in a Real-World Case Series

Authors: Argyro Papadopoulou; S. Stavros; G. Tournas; A. Potiris; K. Filiagkos; S. Khaled; S. Anysiadou; P. Panagopoulos; P. Drakakis; G. Daskalakis; E. Domali

Caesarean scar pregnancy (CSP) is a rare complication that occurs after a previous caesarean delivery and lacks a standardized treatment approach because available evidence is limited. Ultrasound-guided intragestational methotrexate (MTX) injection has been proposed as a fertility-preserving treatment, while systemic methotrexate alone is considered less effective.

This retrospective single-center case series evaluated the efficacy and safety of ultrasound-guided intragestational methotrexate injection in women with caesarean scar pregnancy. The study included 44 consecutive cases managed at a public tertiary referral center between June 2018 and December 2025. Clinical characteristics, ultrasound findings, laboratory results, treatment, and in-hospital outcomes were reviewed. The women had a mean age of 33.1 ± 6.4 years and a mean body mass index of 24.8 ± 4.2 kg/m². The mean gestational age at diagnosis was 8.0 ± 2.6 weeks. Nearly half of the women (46%) were asymptomatic, while 36% presented with bleeding and 18% with both pain and bleeding. Fetal cardiac activity was present in 22 cases (50%).

 Five women were managed expectantly, one underwent hysterectomy, and one was lost to follow-up. The remaining 37 women (84%) received ultrasound-guided intragestational methotrexate injection. Of these, 29 received the standard dose (50 mg/m²) and 8 received a half dose (25 mg/m²) after one case of severe toxicity with the full-dose regimen. A decline of at least 15% in beta-human chorionic gonadotropin (β-hCG) levels between days 4 and 7 was achieved in 33 of 37 women (89%). Four women in the full-dose group did not meet this response criterion and experienced an initial flare-up. Two of these women underwent vacuum aspiration, one required admission to the high dependency unit, and one was managed expectantly. The mean time to undetectable β-hCG levels was 95.3 ± 35 days in the full-dose group and 112.2 ± 38.3 days in the half-dose group, with no significant difference between the groups (p=0.26). The study was limited by its small sample size and single-center design. In addition, the study population included many socioeconomically disadvantaged women who accessed antenatal care later in pregnancy, which may limit the generalizability of the findings.

Overall, ultrasound-guided intragestational methotrexate injection was generally safe and effective for the management of caesarean scar pregnancy, with 89% of treated women achieving the expected early decline in β-hCG levels. The findings support its use as a fertility-preserving treatment option, although larger studies are needed to confirm these results.

ESHRE 2026, July 5^th-8^th, London, UK.