Serum progesterone (P) levels are critical for endometrial receptivity and implantation in frozen-thawed embryo transfer (FET) cycles. However, the prognostic role of P levels measured on the day of the β-human chorionic gonadotropin (β-hCG) pregnancy test has not been fully elucidated. This study aimed to evaluate the association between β-hCG day serum P levels and pregnancy outcomes in FET cycles. This retrospective cohort study included 621 FET cycles performed between January 2023 and December 2024, of which 79.5% were conducted using hormone replacement therapy (HRT) protocols and 20.5% using natural cycle (NC) protocols. Serum P levels were measured on the day of the β-hCG pregnancy test. Receiver operating characteristic (ROC) curve analysis was used to determine protocol-specific P thresholds for predicting ongoing pregnancy (OPR). Ongoing pregnancy was defined as a viable intrauterine pregnancy confirmed by ultrasound at or beyond 12 weeks of gestation. Multivariable logistic regression was applied to identify independent predictors of OPR. ROC analysis identified optimal P thresholds of 15.5 ng/mL in NC cycles (AUC 0.821) and 14.15 ng/mL in HRT cycles (AUC 0.595). Overall, 44% of patients had serum P levels below the protocol-specific threshold. OPR was significantly higher in patients with P levels above the threshold (NC: 63.0% vs. 12.8%; HRT: 48.1% vs. 31.9%; p < 0.001). Multivariable regression demonstrated that younger maternal age and higher β-hCG day P levels independently predicted OPR. In HRT cycles, blastocyst-stage transfer was also significantly associated with improved outcomes (OR = 0.27, 95% CI 0.13–0.59; p < 0.05). Serum P levels measured on the day of the β-hCG test are significantly associated with pregnancy outcomes in both HRT and NC FET cycles. Routine monitoring of late luteal P levels and individualized luteal phase support strategies may enhance clinical success rates.
Objective:Evaluating the therapeutic effect of detorsion, resveratrol, and nifedipine on ovarian viability assessed by biochemical, histopathological and immunohistochemical parameters and markers of oxidative stress. Materials and Methods:Twenty-four Sprague-Dawley rats were included in 4 groups, namely: sham operation, ischemia-reperfusion (I/R), I/R+10 mg/kg nifedipine (NIF), I/R+100 mg/kg resveratrol (RSV). In the study groups, bilateral 720º ovarian torsion was performed and continued for 3 hours, followed by detorsion for another 3 hours. Thirty minutes before the detorsion, NIF and RSV groups received respective treatments. Adnexectomy was performed, and evaluations were made for the expression of anti-müllerian hormone (AMH), vascular endothelial growth factor receptor 2 (VEGFR-2), markers of oxidative stress, and follicle counts. Blood AMH levels were measured. Results:No change in AMH levels was detected. Although the expression of AMH was significantly reduced following I/R alone, it remained similar to the control group in the NIF group. Meanwhile, the RSV group exhibited slightly lower expression than the control, although it was still higher than that observed with the I/R injury group. VEGFR-2 staining was similar in the I/R and NIF groups, but reduced in the RSV group. Markers of oxidative stress were similar between groups. Primordial follicle count was lower in the untreated I/R injury group compared to the control group (p<0.05). The NIF group had more secondary follicles than the I/R injury and RSV groups (p<0.05). Conclusion:Nifedipine and resveratrol treatments did not influence AMH levels and antioxidant-oxidant system parameters in rats exposed to I/R injury. However, nifedipine had a positive effect on AMH expression and secondary follicle count, and resveratrol decreased the expression of VEGFR-2 in tissues, which can be an indicator of their clinical potential.
What is the effect of estradiol (E2) concentrations prior to progesterone administration on pregnancy outcomes? Moderate E2 levels may optimize pregnancy outcomes Estrogen is crucial for endometrial remodeling and receptivity. Studies have shown that high or low peak E2 levels affect pregnancy rates in different ways. However, there is no established E2 level range prior to progesterone administration in FET cycles. While some studies have reported a potential negative correlation between high E2 levels and live birth rates, others have found no significant relationship. This discrepancy underscores the need for further research on the effects of elevated E2 levels in different treatment protocols, as patient responses vary and the underlying mechanisms are not well understood. This retrospective cohort study evaluated 2,122 FET cycles from 1,449 patients who underwent treatment between January 2019 and May 2024. In all HRT-FET cycles, only day 5 blastocyst-stage embryos graded ≥3BB were selected for transfer. E2 levels were categorized into quartiles, with the 25th and 75th percentiles used as cut-off points to assess their association with live birth rates and clinical pregnancy rates. Three groups were formed based on E2 quartiles: Group 1 (≤184 pg/mL), Group 2 (185–295 pg/mL), and Group 3 (≥296 pg/mL). The demographic and cycle-related parameters, pregnancy rates were compared between these groups. Variables with significant differences were included in the regression analysis as confounding factors to predict pregnancy. Statistically significant differences in mean age, BMI, and number of embryo transfers (ET) were observed between the groups (p < 0.05). Patients in Group 1 (31.4 ± 5.1) were younger than those in Group 2 (32.1 ± 5.2) and Group 3 (32.8 ± 5.4) (p = 0.001). The mean BMI in Group 1 (23.6 ± 3.4) was significantly lower compared to Group 2 (24.3 ± 4.1) and Group 3 (24.0 ± 4.2) (p = 0.024). The single ET rate (40.3%) was significantly higher in Group 1 compared to Group 2 (32.1%) (p = 0.010). The ongoing pregnancy rate (OPR), clinical pregnancy rate (CPR), and miscarriage rate did not significantly differ between the E2 groups. Group 2 had the highest OPR (41.4%), followed by Group 1 (40.6%) and Group 3 (36.0%). Generalized estimating equation (GEE) regression analysis, using Group 3 as the reference, revealed that moderate E2 levels (Group 2) (OR [95% CI]: 1.25 [1.06 - 1.57], p < 0.05) and age (OR [95% CI]: 0.98 [0.96 - 0.99], p < 0.05) were independent predictors of pregnancy outcomes. Our findings indicate that moderate E2 levels are associated with more favorable pregnancy outcomes compared to both excessively high and low E2 levels. The main limitations of our study are its retrospective design and the lack of a definitive cut-off value for E2 levels in FET cycles. Therefore, we used interquartile ranges, similar to many other studies. Our findings is consistent showing the impact of E2 levels on pregnancy rates in HRT-FET cycles. Optimizing E2 levels during HRT-FET cycles to avoid excessively high concentrations could help improve suboptimal outcomes. No
ObjectivesHormone replacement therapy (HRT) frozen embryo transfer (FET) cycles are common in assisted reproductive techniques. As the corpus luteum is absent in these cycles, luteal phase support is provided by administering progesterone (P4) through transvaginal, parenteral, or oral routes. Low serum levels of P4 (below 9-10 ng/mL) on the day before embryo transfer (ET) have been associated with unfavorable cycle outcomes. The aim of this study is to investigate whether individualizing luteal support through rescue protocols in patients with low serum P4 levels improves pregnancy outcomes in HRT-FET cycles.Material and methodThis retrospective, single-center cohort analysis includes 1257 cycles involving 942 patients undergoing HRT-FET. Starting in 2019, we have assessed P4 levels before ET day and adjusted MVP doses when P4 levels were <10 ng/mL. In 2021, subcutaneous (SC) P4 was routinely added alongside MVP, with SC doses increased if P4 levels were <10 ng/mL. In this study, Groups 1 and 2 received MVP for luteal support, while Groups 3 and 4 received additional SC progesterone. For patients with P levels below the cut-off level (10 ng/mL) in Groups 2 and 4, the P dose was doubled through a rescue protocol.ResultsIn the MVP and MVP plus SC groups, 15.8% and 8.9% of the cycles had P4 levels <10 ng/mL, respectively. Ongoing pregnancy rates (OPR) and clinical pregnancy rates (CPR) did not differ between study groups. Regression analysis with a mixed model revealed that age, endometrial thickness, and estradiol levels were confounding factors as well as independent predictors of ongoing pregnancy rates (p<0.05). Pairwise regression analysis revealed no significant differences in pregnancy rates between the groups (p>0.05).ConclusionIndividualizing luteal phase support based on serum P4 levels on the day of ET in FET cycles with HRT may enhance pregnancy outcomes by either doubling the vaginal dose or increasing the SC dose during MVP plus SC administration. The implemented rescue protocol allowed patients with low progesterone levels to achieve pregnancy outcomes similar to those with higher progesterone levels.
Does progesterone (P) levels measured on the day of the pregnancy test affect pregnancy outcome in frozen-thawed embryo transfer (FET) cycles? Cycles with higher P levels on the day of the pregnancy test showed significantly better pregnancy outcomes. P levels are the most important biochemical marker for luteal phase support in FET cycles, with several studies indicating that high mid-luteal P levels are associated with better pregnancy outcomes. However, previous studies have primarily evaluated serum P levels on the day of embryo transfer (ET) and have recommended threshold values for clinical practice. Despite the high variability of P, all recent studies on luteal serum P have demonstrated that low serum P levels are linked to poorer cycle outcomes, regardless of the assessment day. There is limited research evaluating P levels on the hCG day. This retrospective study evaluated 656 FET cycles, including 64.3% using hormone replacement therapy (HRT) and 35.7% using natural cycle protocols, between January 2023 and May 2024. The threshold value of serum P on the pregnancy test day to predict ongoing pregnancy was calculated using ROC curve analysis, and patients were divided into two groups. Demographic characteristics, cycle-related indicators, and pregnancy outcomes were compared between the groups. ROC analysis revealed a threshold of 15.5 ng/mL, demonstrating 60% sensitivity and specificity (AUC 0.634; CI 0.591-0.677, p = 0.001). When HRT and natural cycles were analyzed separately, the ROC curves showed similar values. In 47.3% of cycles, P levels were below the calculated threshold (15.5 ng/mL). Ongoing pregnancy rates (OPR) were higher in the group with P levels above this threshold (52.0% vs. 33.5%, p = 0.001). In the low P group, BMI was higher (26.5 ± 5.6) compared to the high P group (24.4 ± 4.6) (p = 0.001). Additionally, patients in the high P group were older (34.6 ± 6.2) compared to those in the low P group (33.7 ± 6.0) (p = 0.045). Significantly different confounding factors, such as age and BMI, were assessed using generalized estimating equation (GEE) regression analysis. The results revealed that only age (OR [95% CI] = 0.88 [0.88 - 0.92], p < 0.001) and P levels on the day of hCG testing (OR [95% CI] = 0.29 [0.19 - 0.45], p < 0.001) were independent predictors of ongoing pregnancy. The main limitation of the study is its retrospective design, along with the exclusion of variations in luteal phase support protocols. The P level measured on the day of the hCG test has been found to be associated with positive pregnancy outcomes. Our findings indicate that continuous monitoring of P levels after pregnancy is achieved, and administering rescue doses when necessary, may have a positive impact on improving pregnancy outcomes. No
Background/aim:Cesarean section (CS) is a widely performed operation worldwide but data about uterine closure are lacking. We aimed to evaluate scar niches and compare single-layer and double-layer uterine closure at 6 months following CS. Materials and methods:This prospective randomized trial assessed 56 women undergoing single- or double-layer uterine closure. None of the patients had previous uterine surgery and all CS cases were elective. Transvaginal ultrasound was performed 6 months after CS to assess the uterine scars by measuring the width, depth, and length of the scar niche and residual myometrial thickness. An experienced sonographer was blinded to the uterine closure technique and the ultrasounds were conducted by practitioners unaware of the technique in the postoperative follow-up appointments. Results:Twenty-eight women were assigned to the single-layer closure group (Group 1) and 28 were assigned to the double-layer closure group (Group 2). The demographic and clinical characteristics of patients and the width, depth and diameter of the niche were similar between the groups, as was residual myometrial thickness. There was no difference in uterine scar volume under the incision between the two groups. The duration of surgery was approximately 5 min longer (p = 0.048) and hemoglobin decrease was about 0.5 g/dL less (p = 0.039) in the double-layer group compared to the single-layer group. Postmenstrual spotting rates were similar between the groups. Group 1 had two and Group 2 had one spontaneous pregnancy within 6 months after CS. Conclusion:The single- and double-layer closure techniques do not produce different impacts on CS niche features at 6 months after delivery. Ultrasound might be an important noninvasive diagnostic tool for understanding CS scar remodeling.
Objective: The cause of implantation defects in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) has not been clearly established.We aimed to evaluate the immunohistochemical changes in HOXA-11, β1 integrin, focal adhesion kinase (FAK), cluster of differentiation 44 (CD44), and extracellular matrix protein 1 (ECM1) molecules during the receptive endometrial period in patients with RIF and RPL. Materials and Methods:This study was retrospectively conducted at a university hospital.After the exclusion of cases with pathology that may cause a change in the level of receptors in the endometrium, biopsies performed during the receptive period were selected, and the patients were categorized into RPL (n=15), RIF (n=16), control (n=16) groups.All preparations were immunohistochemically stained for HOXA-11, β1 integrin, FAK, CD44, and ECM1.Results: HOXA-11 and β1 Integrin expression changes were similar between the RIF and control groups.However, FAK expression was significantly increased in the RIF group (p<0.01).Additionally, ECM1 and CD44 expressions were significantly decreased in the RIF group compared with the control group (p<0.01).There was no significant difference in the endometrial staining of HOXA-11, FAK, and ECM1 in patients with a history of RPL.However, β1 Integrin and CD44 levels were significantly decreased in the RPL group compared with the control group (p<0.05). Conclusion:Implantation is a complex process, and altered adhesion mechanisms involved in endometrial receptivity may be related to defective implantation in patients with RIF and RPL.Among the adhesion molecules, the expression of CD44, β1 integrin, FAK, and ECM1 molecules varies in inappropriate implantation compared with the normal population.
This study aims to analyze the experience of a tertiary health center about the management of adnexal masses that have been diagnosed during pregnancy or detected accidentally during cesarean delivery. This is a retrospective review of 160 women who underwent concurrent surgery for adnexal mass during cesarean section, 24 women who delivered vaginally and subsequently had surgery due to the prenatal diagnosis of adnexal mass and 10 women who underwent surgery for adnexal mass during pregnancy. Corresponding to the delivery and surgery times, 200 women who had no diagnosis of pregnancy-associated adnexal mass served as controls. The women in the control group and study groups had statistically similar gestational age at delivery, birth weight and preterm delivery (p > 0.05 for all). Miscarriage was significantly more frequent in women undergoing surgery for adnexal mass during pregnancy (p = 0.001). The women who had surgery for adnexal mass during pregnancy, at the time of cesarean section and following delivery were statistically similar with respect to surgery type and histopathological diagnosis (p > 0.05 for both). Malignancy was detected in none of the patients who underwent surgery for adnexal mass during pregnancy. Acute abdomen was the indication for the emergency surgery in six patients (3.5
Objective: The principal objective was to compare the diagnostic accuracy of two-dimensional transvaginal ultrasonography (2D TVUS), three-dimensional transvaginal ultrasonography (3D TVUS), and hysteroscopy with histopathology in patients with abnormal uterine bleeding. Materials and Methods: Fifty patients were included and underwent the three imaging methods. The negative predictive value, positive predictive value, sensitivity, and specificity of the methods were calculated. Determination of endometrial pathology and endometrial polyps by measuring the endometrial thickness, volume, and uterine area was examined. Results: The complaint of menorrhagia was reported by 72.0% of participants. Histopathologically, 70.0% of the patients had endometrial polyps and leiomyoma being monitored. An endometrial polyp was detected in 58.0% of the patients by 2D TVUS, 80.0% by 3D TVUS, and 68.0% by hysteroscopy. While 2D TVUS demonstrated 65.71% accuracy in the detection of an endometrial polyp, 3D TVUS had an 80.0% accuracy, and hysteroscopy had a 77.77% accuracy. An endometrial polyp was detected when the uterine area was ≥237 mm2. If the endometrial thickness was over 10.5 mm, it was found to be related to an endometrial polyp. According to the volume measurements by 3D TVUS, the detection of an endometrial polyp was made with 96.4% sensitivity, provided that the pathology volume was ≥0.082 cm3. Conclusion: In this cohort of patients, 3D TVUS achieved a high sensitivity to detect abnormalities and could be considered as an initial diagnostic modality, prior to the surgery, and may rival invasive procedures, such as hysteroscopy.
Objectives Embryo transfer(ET) technique aims to minimize the risk of embryo misplacement and cervical or endometrial trauma. Several factors (operator experience, appropriate catheter choice, ultrasound-guided ET, pharmacological interventions for uterine contractility) affect the success of the procedure. Among those, the impact of ET procedure on the success of IVF has been assessed before in mostly retrospective studies and higher clinical pregnancy rates have been reported with soft compared to firm catheters. But study populations in these reports are not homogeneous as regard to other factors related to success (i.e. fresh or thawed ET). We aimed to update the data on the effect of ET catheters on IVF success by evaluating in a homogeneous group of cycles in which only frozen-thawed day 5 embryos were transferred. Material-Methods In this study, the pregnancy outcomes of transfers using soft catheters (Wallace Classic SureView or Alwinn Echo Soft) and transfers using firm catheters (Wallace Classic SureView markable styled or Allwin Eccitrans Flexible Guide Firm) were compared retrospectively. The primary outcome was the clinical pregnancy rate, while the secondary outcome was the ongoing pregnancy rate. 1224 cycles from patients aged 18-40 years in which frozen-thawed embryo transfer cycles of elective single ET (e-SET) and elective double ET (e-DET) were selected in order to standardize other fresh cycle factors affecting pregnancy rates. Furthermore, only cycles involving frozen-thawed embryos on the 5th day were included to optimize embryo effect on pregnancy outcomes. In addition, all embryo transfers in the study population were performed by the same two experienced clinicians and variants of the same brand of catheters were used. Clinical pregnancy and ongoing pregnancy data were obtained from the clinic's medical record system. The collected data were statistically analyzed using SPSS 25.0. Results A total of 1224 cycles of 785 couples were analyzed. The clinical pregnancy rates for 967 cycles using soft ET catheters and 256 cycles using firm ET catheters were 45.9% and 43%, respectively (p>0.05). The ongoing pregnancy rates for cycles using soft and cycles using firm ET catheters were 36.8% and 32.8%, respectively (p>0.05). Thus, there were no statistically significant difference in the clinical and ongoing pregnancy rates of cycles using either soft or firm ET catheters. The weakness of our study was the retrospective design. However, the high number of cycles, the selection of only day 5 thawed cycles and optimization of inter-operator variability were the strong features of our study. For these reasons, potential factors other than catheter type that might affect the pregnancy rate were minimized. Conclusion The similar clinical and ongoing pregnancy rates observed between ETs using either soft or firm catheters may eliminate the concern about the effect of catheter type on pregnancy outcomes in IVF cycles.
PurposeTo evaluate the impact of serum LH levels prior to progestin administration on the outcomes of programmed frozen-thawed embryo transfer (FET) cycles.MethodsRetrospective cohort study was conducted to compare the treatment outcomes between four groups based on the 25 percentiles of serum LH levels before progestin administration in 596 cycles of 518 patients undergoing artificial endometrial preparation protocols for FET. Primary outcome measures were ongoing and live birth rates. Secondary outcome measures were the pregnancy rates, clinical pregnancy rates, and pregnancy loss rates.ResultsThe trends in clinical pregnancy (CPR) and live birth rates (LBR) increased from the first to the fourth quartile (Q1 to Q4) of serum LH levels prior to progestin administration (37,0% to 48,3%, p = 0.042, and 22.6% to 39.5%, respectively, p = 0.003). Pregnancy loss rates (PLR) were higher in group Q1, although the difference was not statistically significant. Based on a multivariate logistic regression analysis, a low serum LH level before progestin initiation was found to be the most significant predictor associated with a negative effect on live birth (OR: 0,421, 95% CI 0,178 – 0,994, p=0,048). The day of estrogen initiation was significantly correlated with serum LH levels and quartiles of serum LH levels before progestin administration (r=0,200, p=0,015 and r=0,215, p=0,009, respectively).ConclusionThe serum LH level prior to progestin administration significantly affects pregnancy and live birth rates in patients undergoing an artificial endometrial preparation protocol for FET. LH monitoring should be incorporated into the follow-up, in addition to assessing endometrial thickness and morphology in artificial FET cycles.
Objective: It is likely that the subgroups of the epidermal growth factor/platelet-derived growth factor (EGF/PDGF) signaling pathway play a role in the etiopathogenesis of intrauterine growth restriction (IUGR). This study was planned to understand the molecular genetic level of apoptosis in IUGR. Method: The EGF/PDGF signaling pathway gene profile (40 genes) was investigated using a real-time reverse transcriptase-polymerase chain reaction. The gene expressions of the IUGR group were compared both individually and as a group. Individual gene differences were also evaluated. The genes related to cell survival and growth, which include the gene groups of apoptosis, cell cycle, cell differentiation, cell growth, cell motility, and cell proliferation, were investigated using microarray technology. Results: Parity, gestational age at delivery, and APGAR scores at the first and fifth minutes were not significantly different between the IUGR and control groups. However, the women in the IUGR group were younger and slimmer. PRKCA was the only gene with a significant difference in expression between the IUGR and control groups. Nevertheless, individual differences were detected in gene expression associated with cell cycle, differentiation, growth, motility, proliferation, and apoptosis. Conclusion: Variations in gene expression during pregnancy cause changes in placental and fetal development by affecting apoptosis and cellular events at different levels. The genetic causes of IUGR can be revealed by investigating these metabolic pathways. This study differs from previous IUGR studies, which focused on one or a few genes, because all the gene groups in the EGF/PDGF pathway that may be associated with IUGR were investigated.
Objectives To evaluate whether the dual trigger of ovulation with a gonadotropin-releasing hormone (GnRH) agonist and the standard dose of recombinant human chorionic gonadotropin (hCG) (dual trigger) is better than hCG alone in in vitro fertilization (IVF) cycles of patients who responded well to ovarian stimulation. Methods Between January 2013 and December 2021, 5593 antagonist cycles of patients were reviewed. This study included women who had an antral follicle count of 5 or more and exhibited a normoresponse to ovarian stimulation using the GnRH antagonist protocol, as determined by the follicular output rate (FORT). The primary outcome indicators consisted of the quantities of retrieved oocytes and mature oocytes. The secondary outcome markers included live birth rates, clinical pregnancy rates, and continued pregnancy rates. Results A total of 1244 normoresponder women who met the inclusion criteria were identified from the scanned files and subsequently enrolled in the GnRH antagonist protocol. A total of 383 cycles were observed in the group that was given the standard hCG trigger while 861 cycles were observed in the group that was given the dual trigger. The number of mature oocytes and top-quality embryos was significantly higher in the dual trigger group. The maturation rate in the hCG group was 74.8% while it was 76.9% in the dual trigger group (p=0.018). The dual trigger group exhibited an ongoing pregnancy rate of 37.6%, whereas the hCG group had a rate of 30.1% (p = 0.02). The dual trigger group exhibited a slightly higher live birth rate (34.3% vs 29.2%, p = 0.11), although this difference did not reach statistical significance. Conclusion Dual trigger of ovulation was superior to hCG alone in terms of the number of mature oocytes yielded, top quality of embryos, maturation rates, and ongoing pregnancy in IVF cycles of normoresponders having ovarian stimulation on the GnRH antagonist protocol.
Objective: Preeclampsia (PE) is a serious and common pregnancy issue.There is a systemic inflammation in PE and it is accompanied by increased oxidative stress, but the clear etiology has not been revealed.We aimed to predict PE with the systemic immune-inflammation index (SII) value calculated in the first trimester.Material and methods: This is a retrospective study.One hundred fifty-seven pregnant women were included in the study.Twenty-seven pregnant women were excluded from the study.Age, gravida, parity, and hemogram values were recorded in the patients' first visit file records.The time and mode of delivery, birth weight, and APGAR scores were obtained from the file records of the patients.SII was created using the formula (neutrophil x platelet/lymphocyte).Result: The study group included 30 pregnant women who had been diagnosed with PE.The control group consisted of the remaining 100 pregnant women.There was a statistically significant difference between PE and control groups in terms of SII (p=0.03).The SII level cut-off value for predicting PE was determined to be 836.83.This value's area was found to be 0.635 (0.519-0.752).Furthermore, the selectivity is 0.60 and the sensitivity is 0.40 for these values.Conclusion: SII was found to be significantly higher in people with PE in the study.We showed that the SII value measured in the first trimester can be used to predict PE.It might make sense to combine this marker with the patient's history and other risk factors due to its low selectivity and sensitivity.