Ercan Bastu

Flexible progestin-primed ovarian stimulation is a safe and effective alternative to GnRH antagonist protocol in PGT-A cycles - Turkish Journal of Obstetrics and Gynecology

Objective: The study aimed to investigate familial transmission patterns in women with endometriosis by generating a customized single‐nucleotide polymorphism (SNP) array. Methods: Patients aged 18–45 who were diagnosed histopathologically with endometriosis were included in the study. Daughters and mothers of these patients were also included, regardless of whether they were diagnosed with endometriosis or not. The control group consisted of female patients of similar ages who were not diagnosed with endometriosis. The first stage of this investigation was the determination of the genes associated with the SNPs through meta‐analyses in the field of endometriosis in the literature. The second stage was the creation of a unique SNP array by determining the SNPs in the selected target genes. We specifically evaluated whether SNPs in the WNT4 gene at locus 1p36.12 (rs7521902), the GREB1 gene at locus 2p25.1 (rs13391619), and the FN1 gene at locus 2q35 (rs1250248) were associated with endometriosis risk in the Turkish population. Results: The study included 91 participants, comprising 66 women diagnosed with endometriosis and 25 healthy controls. The analysis revealed statistically significant associations for the FN1 (rs1250248, G>A) and the GREB1 (rs13391619, T>C) variants among endometriosis patients and their mothers and daughters, indicating a possible familial genetic link. Conclusion: These findings strengthen the evidence for a hereditary component in endometriosis and suggest that SNP‐based genetic profiling may support earlier identification of at‐risk individuals, enabling more timely surveillance and clinical intervention.

BACKGROUND: The ovarian response to gonadotropin stimulation varies widely among women, and could impact the probability of live birth as well as treatment risks. Many studies have evaluated the impact of different gonadotropin starting doses, mainly based on predictive variables like ovarian reserve tests (ORT) including anti-Müllerian hormone (AMH), antral follicle count (AFC), and basal follicle-stimulating hormone (bFSH). A Cochrane systematic review revealed that individualizing the gonadotropin starting dose does not affect efficacy in terms of ongoing pregnancy/live birth rates, but may reduce treatment risks such as the development of ovarian hyperstimulation syndrome (OHSS). An individual patient data meta-analysis (IPD-MA) offers a unique opportunity to develop and validate a universal prediction model to help choose the optimal gonadotropin starting dose to minimize treatment risks without affecting efficacy. OBJECTIVE AND RATIONALE: The objective of this IPD-MA is to develop and validate a gonadotropin dose-selection model to guide the choice of a gonadotropin starting dose in IVF/ICSI, with the purpose of minimizing treatment risks without compromising live birth rates. SEARCH METHODS: Electronic databases including MEDLINE, EMBASE, and CRSO were searched to identify eligible studies. The last search was performed on 13 July 2022. Randomized controlled trials (RCTs) were included if they compared different doses of gonadotropins in women undergoing IVF/ICSI, presented at least one type of ORT, and reported on live birth or ongoing pregnancy. Authors of eligible studies were contacted to share their individual participant data (IPD). IPD and information within publications were used to determine the risk of bias. Generalized linear mixed multilevel models were applied for predictor selection and model development. OUTCOMES: A total of 14 RCTs with data of 3455 participants were included. After extensive modeling, women aged 39 years and over were excluded, which resulted in the definitive inclusion of 2907 women. The optimal prediction model for live birth included six predictors: age, gonadotropin starting dose, body mass index, AFC, IVF/ICSI, and AMH. This model had an area under the curve (AUC) of 0.557 (95% confidence interval (CI) from 0.536 to 0.577). The clinically feasible live birth model included age, starting dose, and AMH and had an AUC of 0.554 (95% CI from 0.530 to 0.578). Two models were selected as the optimal model for combined treatment risk, as their performance was equal. One included age, starting dose, AMH, and bFSH; the other also included gonadotropin-releasing hormone (GnRH) analog. The AUCs for both models were 0.769 (95% CI from 0.729 to 0.809). The clinically feasible model for combined treatment risk included age, starting dose, AMH, and GnRH analog, and had an AUC of 0.748 (95% CI from 0.709 to 0.787). WIDER IMPLICATIONS: The aim of this study was to create a model including patient characteristics whereby gonadotropin starting dose was predictive of both live birth and treatment risks. The model performed poorly on predicting live birth by modifying the FSH starting dose. On the contrary, predicting treatment risks in terms of OHSS occurrence and management by modifying the gonadotropin starting dose was adequate. This dose-selection model, consisting of easily obtainable patient characteristics, aids in the choice of the optimal gonadotropin starting dose for each individual patient to lower treatment risks and potentially reduce treatment costs.

Embryo migration is defined as the movement of embryos to implant at the exact site in the endometrial cavity during assisted reproductive technology (ART). We aimed to evaluate the impact of embryo migration on clinical pregnancy (CPR) and live birth rates (LBR) in fresh oocyte donation (OD) cycles. A total of 611 fresh OD cycles was recruited in this prospective cohort study. All embryos were expulsed to upper-middle uterus between 10 and 20 mm from the fundus. Air bubble-fundus distance was measured using ultrasound (USG) at the time of embryo transfer (ET) and then 60 minutes after ET. Patients were divided into 3 groups; first group consisted of patients whose embryos migrated towards fundus, second group whose embryos remained between 10 and 20 mm from fundus and the third group including embryos which migrated towards cervix. There was no significant difference between the groups regarding CPR and LBR (p = 0.359 and p = 0.865, respectively). Our study revealed that embryo migration was a fact and almost 22% of embryos migrated towards the fundus or the cervix. On the other hand, whether the embryo stayed static or migrated, CPR and LBR did not differ significantly in fresh OD cycles.

Uterine leiomyomas, also known as fibroids or myoma uteri, are the most common benign pelvic tumor in women. They are monoclonal tumors arising from the smooth muscle cells and fibroblasts of the myometrium. Uterine leiomyomas are usually diagnosed in reproductive-aged women. Determination of the actual prevalence is so difficult because of heterogenous presentation of the disease. Although women having uterine leiomyomas may suffer from abnormal uterine bleeding, pelvic pain, pelvic mass, infertility, and obstetric complications, others remain asymptomatic. Approximately one-third of women with uterine leiomyomas will demand treatment depending on the severity of their symptoms Another important issue during management of myomas is the patient’s desire for immediate or future childbearing as the therapeutic approaches result in different impacts on fertility. According to localization of uterine leiomyomas, surgical routes may differ in terms of hysteroscopy, laparoscopy or laparotomy. With recent advances in technical developments and increased surgical experiences, laparoscopic myomectomy has started to be preferred for many reasons such as less blood loss and pain, lower complications and adhesion formation, faster post-operative recovery, and shorter duration of hospital stay. The number, size, and location of the fibroids are important factors during decision of laparoscopic or open technique. Despite limited data in literature, different routes have no impact on live birth rate.

Aim To compare the pregnancy outcomes between physiologic saline and G-Rinse medium solution for cervical mucus washing, in fresh elective single-embryo transfers (ET) in women under the age of 37. Material and methods This was a retrospective data analysis performed in a single in vitro fertilization (IVF) center between February 2018 and November 2021. Women younger than 37 years who underwent single elective ET were included and all women had anti-Mullerian hormone (AMH) levels ≥ 1.5 ng/ml. Age, body mass index (BMI), AMH levels, and pregnancy outcomes as clinical pregnancy rate (CPR) and live birth rate (LBR) were analyzed. Results Study population consisted of 75 women in the G-Rinse medium solution group and 97 women in the physiologic saline group. Clinical pregnancy rate was 58.7% and 61.9% in the G-Rinse medium solution group and saline group, respectively (p = 0.673), and LBR was calculated as 41.3% and 47.4% in the G-Rinse medium solution group and saline group, respectively (p = 0.430). A log-binomial regression model was used and the model was adjusted for BMI to evaluate the effect of the cervical mucus washing method on the pregnancy outcomes. There was an estimated 5% decrease in the relative risk for CPR in the G-Rinse medium solution group compared to the saline group (95% CI: 0.74 to 1.2, p = 0.673). There was an estimated 13% reduction in the relative risk for LBR in the G-Rinse medium solution group compared to the saline group (95% CI: 0.62 to 1.23, p = 0.430). They were both statistically not significant. Conclusion In our study, the replacement of using G-Rinse medium solution to physiologic saline solution for cervical cleaning did not change CPR and LBR outcomes. Using physiologic saline solution can be a good alternative approach for ectocervical washing during embryo transfer in selected population because of its lower costs, easy accessibility, and common use.

This study aims to understand differences/similarities in the genetic profile of the endometrium at the start of window of implantation (WOI) in women with unexplained infertility (UI) and unexplained recurrent pregnancy loss (uRPL). Differentially expressed genes (DEGs) from the endometrium were evaluated using gene expression array and pathway enrichment analysis was performed to analyse gene expression pathways involved in both conditions. We found 2,171 genes arranged in 117 pathways and 730 genes arranged in 33 pathways differentially expressed in endometrium of patients in UI and uRPL, respectively. Complement-coagulation cascades, morphine addiction pathway, and PI3K-Akt signalling pathway were predominantly differentially expressed in UI. Cancer pathways, NF-κB signalling pathway, and actin cytoskeleton regulation pathway showed significant changes in uRPL. Forty-eight percent of DEGs and 84% of differentially expressed pathways in uRPL were found in the endometrium of UI patients. Unexpected close association in gene expression pathways between UI and uRPL is observed supporting the hypothesis ‘uRPL is a clinical subset of UI’. Yet 100% DEGs overlap wasn’t found suggesting the endometrium has still some different gene expression patterns at start of WOI in UI and uRPL. Lastly, diagnostic tools may be developed for uRPL because more specific genes-pathways are involved compared with UI, which shows broader genetic expression profile.

Endometrial thickness (ENT) measurements are important to evaluate endometrial receptivity. The effect of endometrial thickness on pregnancy outcomes has been discussed for many years with conflicting results. The aim of our study was to find out the effect of endometrial thickness (ENT) change in response to progesterone on pregnancy outcomes in embryo transfer (ET) of fresh oocyte donation (OD) recipients. The study was designed retrospectively including 134 embryo transfers with fresh OD recipients. ENT was measured by ultrasonography (USG) on the day of initial progesterone administration (ENT1) and on ET day (ENT2). The primary outcome was to determine any correlation between the ENT change and pregnancy outcomes. ENT increased in 56.7% of cases and decreased in 43.4%. Clinical pregnancy rate (CPR) in recipients with increased ENT was 76.3%, and live birth rate (LBR) was 72.4%. CPR in recipients with decreased ENT was 69.0% and LBR was 65.5%. There was no significant difference between recipients with either increased or decreased ENT regarding CPR and LBR (p = .225 and p = .253, respectively). Our study revealed that ENT change after 6 days of progesterone administration, whether increased or decreased, does not have any significant effect on LBR and CPR in fresh OD recipients.