Clinical Pregnancy Rate In Women Research Articles

Intramural Leiomyomas and Fertility: A Systematic Review and Meta-Analysis.

To evaluate fertility outcomes based on size and number of intramural leiomyomas and outcomes after removal. Online searches: MEDLINE, ClinicalTrials.gov , PubMed, Cochrane Library, and PROSPERO Library from 1994 to 2023. A total of 5,143 studies were identified, with inclusion of 13 study groups. Outcomes for size and number of leiomyomas were reported with clinical pregnancy rates and ongoing pregnancy or live-birth rates. In data sets with maximum leiomyoma diameters of less than 6 cm for study inclusion, women with leiomyomas smaller than 3 cm had lower clinical pregnancy rates than women without leiomyomas, with an odds ratio (OR) of 0.53 (95% CI, 0.38-0.76) and, for ongoing pregnancy or live-birth rates, an OR of 0.59 (95% CI, 0.41-0.86). The ORs for clinical pregnancy rates in women with intermediately-sized leiomyomas (those between 3 cm and 6 cm) were lower than in women without leiomyomas, with an OR at 0.43 (95% CI, 0.29-0.63) and, for ongoing pregnancy or live-birth rates, an OR at 0.38 (95% CI, 0.24-0.59). In data sets without exclusion for women with larger-sized leiomyomas, clinical pregnancy rates were lower for those with leiomyomas smaller than 5 cm compared with those without leiomyomas, with an OR of 0.75 (95% CI, 0.58-0.96). Women with leiomyomas larger than 5 cm showed no differences in clinical pregnancy rate compared with women without leiomyomas, with an OR of 0.71 (95% CI, 0.32-1.58). Although women with a single leiomyoma in any location had no differences in outcomes, those with more than one leiomyoma had lower clinical pregnancy rates and ongoing pregnancy or live-birth rates, with an OR of 0.62 (95% CI, 0.44-0.86) and 0.57 (95% CI, 0.36-0.88), respectively. The clinical pregnancy rate for women undergoing myomectomy for intramural leiomyomas was no different than those with intramural leiomyomas in situ, with an OR of 1.10 (95% CI, 0.77-1.59). Even small intramural leiomyomas are associated with lower fertility; removal does not confer benefit. Women with more than one leiomyoma in any location have reduced fertility.

P-626 Progesterone rescue is effective for clinical pregnancy outcome in women presenting low circulating progesterone levels at frozen embryo transfer day

Abstract Study question Is subcutaneous progesterone (prolutex® 25mg daily) addition effective for clinical pregnancy outcome in women presenting low progesterone(P4) levels at frozen embryo transfer(FET) day? Summary answer Subcutaneous progesterone rescue improved ongoing pregnancy rate and clinical pregnancy rate in women with low P4 results at FET day. What is known already FET has been increased, because preimplantation genetic testing for aneuploidies is performed widely, and FET presents a significantly low risk of ovarian hyperstimulation syndrome.In FET, there is no established optimal protocol for preparing endometrium, but hormonal replacement therapy (HRT) is widely used due to its convenient schedule adjustment. HRT protocol induce anovulation, functioning corpus luteum is lacking and exogenous progesterone administration is very important. Therefore, women showing low P4 levels around FET day have lower pregnancy rate. However, there are currently no data on the effectiveness of progesterone rescue. Study design, size, duration Primary outcomes from a randomized cohort retrospective study investigating subcutaneous progesterone (prolutex® 25mg) daily addition for whom had low P4 levels (<12ng/mL) at FET day. The study was conducted at one infertility center in Korea from January 2022 to December 2023 and pregnancy outcomes of FET transfers registered until Oct. 2023,. 194 patients fulfilled the inclusion criteria. Participants/materials, setting, methods One hundred ninety four women divided into two groups based on progesterone levels, with 12ng/ml as the threshold. Under 12ng/mL group were randomized to subgroup with and without addition of subcutaneous progesterone. In total 278 FET cycles, the effect of progesterone rescue on cumulative clinical pregnancy rate (CPR), Ongoing pregnancy rate (OPR) was reported as primary outcomes. Main results and the role of chance In total 278 cycles, there were 137 cycles with adequate serum P4 levels, while 141 cycles presented with low P4 levels in which randomly rescue subcutaneous progesterone administration added from next day of embryo transfer. When comparing the groups, there was no statistical difference in maternal age, BMI, smokers, duration of infertility, type of infertility, indication of in vitro fertilization(IVF), endometrial preparation method. In low P4 group, with and without subcutaneous progesterone addition subgroups included 51 and 90 cycles, retrospectively. CPR were 52.9% versus 35.6% (P = 0.044; chi-squared test) with a statistically significant higher rate of OPR in progesterone rescue group (45.1% versus 28.9%, p = 0.052). When comparing the group with adequate P4 levels and the group with low P4 levels without progesterone rescue, OPR were 18.2% versus 28.9% (p = 0.06, chi-squared test), CPR was significantly higher in low P4 levels group (23.4% versus 35.6%,p=0.046, chi-squared test). Adequate P4 level group had more IVF attempts (4.6 versus 2.2, p < 0.001, chi-squared test). There is tendency to use more luteal phase support medication with repeated attempt (serum P4 concentration on ET day 39.3 ng/mL versus 8.7 ng/mL, p < 0.001, t-test) Limitations, reasons for caution The main limitation of the study was retrospective, and had small sample size. A control group without progesterone rescue in low P4 levels did not receive any intervention. Wider implications of the findings The progesterone rescue for women presenting low P4 on FET day improved clinical outcome and excessively raising progesterone medication may have adverse effects. Therefore rather than using excessive progesterone administration from luteal support start day, progesterone rescue might be effective when low P4 levels presenting at FET day. Trial registration number not applicable

P-553 Embryo collection improves clinical pregnancy outcomes in next-generation sequencing(NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) euploid embryo transfers

Abstract Study question Is there still a significant impact of embryo-related characteristics on pregnancy rates in NGS based PGT-A euploid embryo transfers for advanced-age patients? Summary answer In single frozen euploid embryo transfers, priority of embryo transfer and grade significantly influence clinical pregnancy rates in women over 35 years old with PGT-A. What is known already It is widely recognized that better embryo grades and a shorter duration of blastulation are associated with favorable reproductive outcomes. Recent meta-analyses have affirmed these findings even in the context of transfer with euploid embryos. However, the impact of prioritizing the highest-ranked embryo among multiple vitrified euploid embryos on pregnancy rates remains unclear. The lack of research in this area implies a gap in understanding whether selecting embryos for transfer among multiple viable euploid embryos could enhance reproductive success. Study design, size, duration Throughout the year 2022, a retrospective review was conducted on 428 cycles of single frozen-thawed euploid embryo transfers performed at a single institution, targeting patients aged 35 and older. The study aimed to explore potential differences in clinical pregnancy rates based on embryo grade, embryo freezing date, and embryo selection priority. Participants/materials, setting, methods Women ≥ 35 years old with single frozen euploid blastocyst transfer cycles was categorized into three groups: (a) with one blastocyst (1/1), (b) with ≥ two blastocysts having the top-priority(½ or higher), and (c) lower-priority blastocysts (lower than ½) to examine potential differences in clinical pregnancy rates among groups based on embryo characteristics, including Gardner grading and day of embryo freezing. Results highlight the impact of both selection criteria and freezing conditions on pregnancy outcomes. Main results and the role of chance This study analyzed a total of 428 frozen embryo transfer (FET) cycles. In the context of frozen-thawed single embryo transfer, the clinical pregnancy rate was 52.2% (128/245) when only one euploid embryo was frozen and subsequently thawed for transfer (a). For cases where two or more euploid embryos were frozen, and embryos with a higher priority (½ or higher) were selected for transfer (b), the clinical pregnancy rate significantly increased to 71.3% (62/87). Conversely, when embryos with a lower priority (lower than ½ in order) were chosen for transfer (c), the clinical pregnancy rate was lower at 38.5% (15/38), indicating a statistically significant difference between the groups (p = 0.001). Categorizing embryos based on Gardner grading, “good” embryos (>3BB) demonstrated a clinical pregnancy rate of 66.8% (141/211), while embryos with lower quality (3BB or below) showed a significantly lower clinical pregnancy rate of 40.6% (88/217) (p < 0.001). The analysis of clinical pregnancy rates based on the embryo freezing day revealed significant differences among embryos freezing on 5 days (71.9%, 133/185), 6 days (39.9%, 71/178), 7 days (25%, 2/8), and thawing PGT-A embryos (38.2%, 21/55) (P < 0.001). Limitations, reasons for caution One limitation of this study is its retrospective nature, and the potential confounding effect of the close association between embryo selection and embryo grading. Further analysis will be conducted to confirm correlations and address this potential confounding effect. Wider implications of the findings In single euploid frozen embryo transfers, selecting the highest-quality embryo through careful embryo selection remains relevant. Morphological indicators of embryos significantly impact early pregnancy outcomes, highlighting the continued importance of strategic embryo accumulation for enhanced procedural success. Trial registration number not applicable

Does Gonadotropin-Releasing Hormone Agonist Administration Before Assisted Reproduction Techniques Improve Pregnancy Rates in Women With Endometriosis?

Axial downregulation with a 3- to 6-month administration of gonadotropin-releasing hormone agonists (GnRH-a) prior to assisted reproduction techniques has been proposed in order to improve clinical pregnancy rates in women with endometriosis. Although reduced inflammation, improved oocyte quality, and restored endometrial receptivity have been postulated, further investigation of their actual benefit and mechanism of action is considered essential. In that direction, well-designed clinical trials regarding the role of GnRH-a in IVF are necessary. The purpose of this review is to clarify whether GnRH-a administration prior to IVF-FET procedures improves pregnancy rates in women with endometriosis. A literature review was conducted in MEDLINE (PubMed), Cochrane, and Google Scholar and concluded on September 10, 2022. Two Cochrane meta-analyses and 16 selected studies present various interesting data of assisted reproduction technique procedures on patients with endometriosis-related infertility with or without depot GnRH-a pretreatment. The regimen may have a positive clinical effect on cases of severe endometriosis (American Society for Reproductive Medicine stages III-IV), but their use is not routinely recommended in order to improve pregnancy rates. Endometriosis and infertility are closely related through various pathogenetic mechanisms. Endometriosis has been traditionally considered to negatively affect fundamental aspects of the in vitro fertilization-frozen embryo transfer procedure. Numerous interventions, both medical and surgical, have been proposed in order to improve IVF success rates, and the optimal management of these cases poses an ever pressing challenge.

Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction.

Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review investigates the adjunct use of synthetic versions of two naturally produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction. Steroid hormones are proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation. This may lead to a greater oocyte yield and, subsequently, an increased chance of pregnancy. To assess the effectiveness and safety of DHEA and T as pre- or co-treatments in infertile women undergoing assisted reproduction. We searched the following electronic databases up to 8 January 2024: the Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries for ongoing trials. We also searched citation indexes, Web of Science, PubMed, and OpenGrey. We searched the reference lists of relevant studies and contacted experts in the field for any additional trials. There were no language restrictions. Randomised controlled trials (RCTs) comparing DHEA or T as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction. Two review authors independently selected studies, extracted relevant data, and assessed risk of bias. We pooled data from studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. We assessed the certainty of evidence for the main findings using GRADE methods. We included 29 RCTs. There were 1599 women in the intervention group and 1469 in the control group. Apart from three trials, the trial participants were women identified as 'poor responders' to standard in vitro fertilisation (IVF) protocols. The included trials compared either T or DHEA treatment with placebo or no treatment. Pre-treatment with DHEA versus placebo/no treatment: DHEA likely results in little to no difference in live birth/ongoing pregnancy rates (OR 1.30, 95% confidence interval (CI) 0.95 to 1.76; I² = 16%, 9 RCTs, N = 1433, moderate certainty evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 12% and 20%. DHEA likely does not decrease miscarriage rates (OR 0.85, 95% CI 0.53 to 1.37; I² = 0%, 10 RCTs, N =1601, moderate certainty evidence). DHEA likely results in little to no difference in clinical pregnancy rates (OR 1.18, 95% CI 0.93 to 1.49; I² = 0%, 13 RCTs, N = 1886, moderate certainty evidence). This suggests that in women with a 17% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using DHEA will be between 16% and 24%. We are very uncertain about the effect of DHEA on multiple pregnancy (OR 3.05, 95% CI 0.47 to 19.66; 7 RCTs, N = 463, very low certainty evidence). Pre-treatment with T versus placebo/no treatment: T likely improves live birth rates (OR 2.53, 95% CI 1.61 to 3.99; I² = 0%, 8 RCTs, N = 716, moderate certainty evidence). This suggests that in women with a 10% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 15% and 30%. T likely does not decrease miscarriage rates (OR 1.63, 95% CI 0.76 to 3.51; I² = 0%, 9 RCTs, N = 755, moderate certainty evidence). T likely increases clinical pregnancy rates (OR 2.17, 95% CI 1.54 to 3.06; I² = 0%, 13 RCTs, N = 1152, moderate certainty evidence). This suggests that in women with a 12% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using T will be between 17% and 29%. We are very uncertain about the effect of T on multiple pregnancy (OR 2.56, 95% CI 0.59 to 11.20; 5 RCTs, N = 449, very low certainty evidence). We are uncertain about the effect of T versus oestradiol or T versus oestradiol + oral contraceptive pills. The certainty of the evidence was moderate to very low, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in the trials. Data on adverse events were sparse; any reported events were minor. Pre-treatment with T likely improves, and pre-treatment with DHEA likely results in little to no difference, in live birth and clinical pregnancy rates in women undergoing IVF who have been identified as poor responders. DHEA and T probably do not decrease miscarriage rates in women under IVF treatment. The effects of DHEA and T on multiple pregnancy are uncertain. Data regarding adverse events were very limited; any reported events were minor. Research is needed to identify the optimal duration of treatment with T. Future studies should include data collection on adverse events and multiple pregnancy.

#311 : Intrauterine Administration of Human Chorionic Gonadotropin in Women Undergoing IVF– An Individual Participant Data Meta-Analysis

Background and Aims: Human chorionic gonadotropin (hCG) has been proposed as an intrauterine intervention around embryo transfer period due to its potential to enhance endometrium receptivity and implantation. Existing randomised controlled trials (RCTs) showed inconsistent findings and multiple meta-analyses on this topic showed high unexplained heterogeneity. Individual participant data meta-analysis (IPDMA) is considered the “gold standard” synthesis method due to its ability to standardise and harmonise the data reporting and analysis. In this IPDMA, we aimed to investigate the effectiveness and safety of intrauterine hCG before embryo transfer. Method: We searched Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase and PsycINFO without language restrictions up to November 2022. We included RCTs comparing intrauterine administration of hCG before embryo transfer versus placebo or no intervention in women undergoing IVF. The outcomes were live birth, clinical pregnancy and other fertility outcomes. We invited trial authors to share the de-identified IPD and established the IHABT collaboration. We performed a one-stage IPDMA as the main analysis. Results: Eight RCTs including IPD of 2338 participants were included. These RCTs were conducted in 6 different countries, with a dosage of intrauterine hCG between 500 IU and 1000 IU. In women undergoing IVF, compared to the control group, intrauterine administration of hCG before embryo transfer does not improve live birth rates (7 RCTs, 2245 participants, odds ratio [OR] 0.98, 95% confidence interval [CI] 0.82–1.17) or clinical pregnancy rates (8 RCTs, 2338 participants, OR 1.13, 95%CI 0.89–1.43). There was insufficient evidence of a difference between the two groups on any of the other fertility outcomes. Conclusion: Intrauterine administration of hCG does not improve live birth or clinical pregnancy rates in women undergoing IVF. Therefore, it should not be offered as an IVF add-on in clinical practice.

Improved Pregnancy Outcomes and Endometrial Receptivity by Thawed Frozen Embryo Transfer in Mildly Stimulated Cycles with Letrozole Combined with Estrogen in Women with Unresponsive Thin Endometrium Compared to Standard Endometrial Preparation with Estrogen Alone: A Retrospective Study.

Infertile women undergoing frozen embryo transfer (FET) cycles may not show optimal endometrial growth with estrogens alone. To evaluate clinical effect of mild stimulation with letrozole and estrogens on endometrial growth in comparison to standard endometrial preparation with oral and topical estrogens in infertile women with unresponsive thin endometrium undergoing FET. Retrospective observational case-control study. Forty women unresponsive to first AC-FET cycle were given mild stimulation with letrozole and estrogens as second LE-FET cycle for endometrial preparation (LE-FET study group) and compared with 40 historical controls who had received two cycles of AC-FET (AC-FET control group). Responses were assessed by optimal endometrial thickness (≥ 7mm) and clinical pregnancy. Descriptive statistics were elaborated by mean ± SD and percentages. Results were expressed by mean ± SD, unpaired t test for difference in endometrial thickness, chi square and Fisher exact test to compare the difference in pregnancy among both groups. Mean endometrial thickness was significantly increased in LE-FET study group (6.68 ± 2.09mm) versus AC-FET control group (5.35 ± 1.90mm). Higher clinical pregnancy rate was noted in study group as compared to control group (35% versus 12.5%). This study suggests that letrozole with estradiol (LE-FET) compared to estradiol alone (AC-FET) for second cycle significantly increased endometrial thickness and improved clinical pregnancy rates in women with unresponsive thin endometrium after first AC-FET cycle with estradiol alone. Addition of letrozole to estrogen upfront for FET cycles may enhance endometrial receptivity and might improve pregnancy outcomes.

Reproductive outcome and gynecologic comorbidities in women with endometriosis in a non-IVF setting: a retrospective study

BackgroundEndometriosis-related infertility is a disease associated with significant morbidity and distress to the couple and requires timely, multidisciplinary, and often high-cost care involving assisted reproductive technologies (ART). Many health care systems in the Middle East do not provide coverage for ART. This study aims to describe the reproductive outcome in a form of a clinical pregnancy rate in women with endometriosis-related infertility in a health care system that does not provide coverage for ART.ResultsThis is a retrospective observational cohort study on women who attended the gynecology clinic in a tertiary center in Oman with the diagnosis of endometriosis from January 2011 to December 2019. Women of reproductive age seeking pregnancy were included in the analysis. Out of total women with endometriosis, (144/262) 55.0% were included in the analysis with a mean age of 31.10 ± 5.73 years. The mean duration of follow-up was 30.18 months and 43/144 (29.9%) of our patients had a follow-up > 60 months. Based on surgical staging, 11.8% had mild disease, 70.1% had moderate to severe disease and 18.1% were not operated. After a thorough assessment, (30.2%) were advised to seek in vitro fertilization (IVF) as a primary treatment for infertility but 23.08% declined the advice. Of the 144, 24.3% achieved a clinical pregnancy. (16/144), 11% conceived spontaneously. 11/144) 7.6% conceived with ovulation induction ± intrauterine insemination (OI ± IUI) and the rest conceived with a self-sponsored IVF. The overall clinical pregnancy rate was not statistically different between those who had surgery and those did not have surgery (P value 0.474). The pregnancy rate based on the management plan were; surgery + IVF (7/25, 28.0%), surgery + OI/IUI (10/47, 21.3%), surgery alone (9/33, 27.3%). The pregnancy rate was not statistically different between the groups (P value 0.782).In addition to endometriosis, a significant proportion (63/144, 43.8%) of these women have a coexisting gynecologic morbidity including 2.1% non-endometrioma ovarian cyst, 13.9% myomas, 4.2% adenomyosis, 8.3% Mullerian anomalies, 2.1% polycystic ovary syndrome, 6.3% pelvic inflammatory disease or tubo-ovarian abscess and 1.4% biopsy-proven endometritis.ConclusionThe reproductive outcome of patients with endometriosis in this study population was generally poorer than what is reported in the literature with an overall pregnancy rate of 24.3% and a spontaneous pregnancy rate of 11%. Several causes can be noted for such an outcome, including advanced disease stage, coexisting gynecologic morbidities, and poor access to advance fertility management.

P-665 Timing of metformin treatment in women with polycystic ovarian syndrome and associated pregnancy outcomes: a systematic review and meta-analysis

Abstract Study question Does giving women with polycystic ovarian syndrome (PCOS) preconception metformin and continuing it through at least the first trimester improve pregnancy outcomes? Summary answer Giving women with PCOS preconception metformin and continuing throughout the first trimester significantly reduces the risk of early miscarriage, and can improve pregnancy outcomes. What is known already Metformin, either alone or in combination with other ovulation induction agents, can improve ovulation and clinical pregnancy rates in women with PCOS. Its impact on miscarriage and live birth rate are less well understood. Furthermore the impact of both the timing and duration of metformin treatment on subsequent pregnancy outcomes, in women with PCOS, is unknown. We sought to evaluate the role that preconception metformin, continued until at least the point of positive pregnancy test, may have on pregnancy outcomes in women with PCOS and the effect that stopping metformin once pregnant might have. Study design, size, duration We conducted a systematic review and meta-analysis. A search within MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for studies listed from database inception to 13th October 2022 was conducted. Potentially eligible studies identified through other sources (such as the reference lists of the selected primary studies and review articles) were also screened for inclusion. We adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) for determining the quality of the evidence. Participants/materials, setting, methods The full-text of studies identified as being potentially suitable for inclusion were obtained. Those meeting the study selection criteria, outlined, were included in the systematic review and meta-analysis. Studies were included if they were prospective randomised controlled trials, comparing the use of metformin in women with PCOS, which had been started pre-conceptually and continued at least until pregnant (confirmed urinary pregnancy test), to either placebo or no treatment. Main results and the role of chance A total of 12 studies (1517 women) were included in the systematic review and meta-analysis. Women who were given preconception metformin which was continued until at least the end of the first trimester showed a significantly reduced risk of early miscarriage [OR 0.51 95% CI (0.27-0.96), 6 studies, n = 294, I2=0%], compared to either placebo or no treatment. Continuing preconception metformin until at least the end of first trimester also significantly increased clinical pregnancy rates [OR 1.92 95% CI (1.43-2.59), 5 studies, n = 793, I2=67%]. Only 3 studies, looked at live birth outcome which showed an increased odds of live birth in the metformin group, but this was not statistically significant [OR 1.38 95% CI (0.65-2.92), 3 studies, n = 212, I2=0%]. In women who stopped taking metformin following a positive pregnancy test, there was a suggestion of improvement in clinical pregnancy [OR 1.36 95% CI (0.99-1.87), 6 studies, n = 663, I2=45%] and live birth rates [OR 1.15 95% CI (0.57-2.35), 5 studies, n = 244, I2=0%]; but these were not statistically significant. Conversely, there was an increased odds of early miscarriage [OR 1.22 95% CI (0.59-2.52), 6 studies, n = 244, I2=0%], but this was also not statistically significant. Limitations, reasons for caution Whilst a role for commencing metformin pre-conceptually and continuing until at least the end of the first trimester has been demonstrated to be effective in improving clinical pregnancy rates and reducing miscarriage risk, the effectiveness and safety of continuing it throughout the remainder of the pregnancy remains unclear. Wider implications of the findings Continuing metformin treatment until at least the end of first trimester can increase the clinical pregnancy rate and reduce the risk of miscarriage. Stopping metformin once pregnant could be harmful and increase the risk of miscarriage. These findings should be considered when managing women with PCOS wishing to conceive. Trial registration number CRD42017073976

Lights and shadows on the use of metformin in pregnancy: from the preconception phase to breastfeeding and beyond.

During pregnancy, the complex hormonal changes lead to a progressive decrease of insulin sensitivity that can drive the onset of gestational diabetes (GDM) or worsen an already-known condition of insulin resistance like type 2 diabetes, polycystic ovarian syndrome (PCOS), and obesity, with complications for the mother and the fetus. Metformin during pregnancy is proving to be safe in a growing number of studies, although it freely crosses the placenta, leading to a fetal level similar to maternal concentration. The aim of this literature review is to analyze the main available evidence on the use of metformin during, throughout, and beyond pregnancy, including fertilization, lactation, and medium-term effects on offspring. Analyzed studies support the safety and efficacy of metformin during pregnancy. In pregnant women with GDM and type 2 diabetes, metformin improves obstetric and perinatal outcomes. There is no evidence that it prevents GDM in women with pregestational insulin resistance or improves lipid profile and risk of GDM in pregnant women with PCOS or obesity. Metformin could have a role in reducing the risk of preeclampsia in pregnant women with severe obesity, the risk of late miscarriages and preterm delivery in women with PCOS, and the risk of ovarian hyperstimulation syndrome, increasing the clinical pregnancy rate in women with PCOS undergoing in vitro fertilization (IVF/FIVET). Offspring of mothers with GDM exposed to metformin have no significant differences in body composition compared with insulin treatment, while it appears to be protective for metabolic and cardiovascular risk.

Is glucocorticoid use associated with a higher clinical pregnancy rate of in vitro fertilization and embryo transfer? A meta-analysis

BackgroundIt has been reported that the use of glucocorticoids may be able to improve clinical pregnancy rates in patients receiving in vitro fertilization and embryo transfer (IVF-ET). The purpose of this study was to investigate the association between glucocorticoid use and clinical pregnancy rate in IVF-ET patients. MethodsThis study has been registered on the International Register of Prospective Systems Evaluation (PROSPERO) (ID: CRD42022375427). A thorough and detailed search of databases including PubMed, Web of Science, Embase, and Cochrane Library was conducted to identify eligible studies up to October 2022. Quality assessment was conducted on the modified Jadad Scoring Scale and Newcastle-Ottawa Scale, and the inter-study heterogeneity was estimated by Q test and I2 test. Combined hazard ratios with 95% CI were calculated using random effects or fixed effects models based on heterogeneity. Meanwhile, Begg's and Egger's tests were used to detect the existence of publication bias, the leave-one-out method was used for sensitivity analysis and multiple subgroup analyses were conducted. ResultsSeventeen studies involving 3056 IVF-ET cycles were included. We found that glucocorticoid use was associated with a higher IVF-ET pregnancy rate (OR = 1.86, 95% CI = 1.27–2.74, P = 0.002). In the subgroup analysis, studies of different regions and different study types all showed similar results that glucocorticoid is beneficial to improve the clinical pregnancy rate of patients with IVF-ET, and patients with positive autoantibodies and patients receiving IVF-ET multiple times also showed the same results. However, there was no significant change in clinical pregnancy rates in the seven studies with negative autoantibodies and in the seven studies with initial IVF-ET treatment. The results of the 12 medium-acting glucocorticoids and 4 long-acting glucocorticoids were also generally consistent with each other. There was no statistical difference in subgroup analysis of whether patients had endometriosis or not. ConclusionAppropriate use of glucocorticoids is beneficial for improving the clinical pregnancy rate in women receiving IVF-ET, but this result still needs to be verified by more high-quality and large sample size randomized controlled trials (RCTs).

Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience.

Repeated embryo implantation failures (RIF) is a source of distress and frustration for patients and clinicians alike. Today's approaches for treating RIF are largely empirical and have limited effectiveness. The main causes of RIF are poor endometrial receptivity and poor-quality embryos. Recent studies have suggested the involvement of immune dysregulation due to an imbalance between T-helper (Th) 1 and Th2 cytokines; this opens up perspectives for treating women with RIF and increasing the implantation rate. We conducted an interventional, longitudinal, prospective cohort study of the impact of correcting the cytokine imbalance on the clinical pregnancy rate in women with RIF. Seventy-seven women with RIF underwent an endometrial biopsy during the implantation window. The cytokine profile was evaluated by studying the activation and maturation of uterine natural killer (uNK) cells, the IL-15/Fn-14 mRNA ratio (a biomarker of uNK activation/maturation), and the IL-18/TWEAK mRNA ratio (a marker of angiogenesis and the Th1/Th2 balance). Personalized treatment was initiated for women with an abnormal endometrial cytokine profile (hyper-activation or hypo-activation). We documented the clinical pregnancy rate after subsequent embryo transfers. In total, 72.7% (56/77) of patients had an abnormal endometrial cytokine profile (hyper-activation in 68.8% (n = 53) and hypo-activation in 3.9% (n = 3). After treatment (or not) as a function of the endometrial profile, the overall clinical pregnancy rate was 30.2%. Our results indicated a potential positive effect of appropriate treatment on the ongoing pregnancy rate in women with RIF, despite the small number of cases analyzed. The results must now be validated in randomized studies with larger numbers of well-characterized patients. By applying a previously published decision tree, this treatment approach could be implemented in clinics worldwide.

Relationship between advanced maternal age and decline of endometrial receptivity: a systematic review and meta-analysis.

Female fertility decreases with age. A decline in oocyte quality plays a key role in reproductive problems in older women. Whether advanced maternal age (AMA) is associated with a decline in endometrial receptivity (ER) remains controversial. A systematic review and meta-analysis were conducted to evaluate the relationship between AMA and ER. Eighteen eligible studies were included in this meta-analysis. Of the 18 studies, 17, 8, 14, and 9 studies reported the impact of AMA on clinical pregnancy rate (CPR), implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR), respectively. The combined results showed a trend (without significance) toward lower CPR in women with AMA than in younger women. A similar trend of worse outcomes in terms of IR was observed in women with AMA. A significantly higher MR and lower LBR were observed in infertile women with AMA than in younger women. In conclusion, there was a slightly lower IR and CPR without significance; however, significantly increased MR and decreased LBR were observed in women with AMA than in younger women, indicating that AMA is related to the decline of ER. Further prospective cohort studies with a preimplantation genetic testing for aneuploidy model are needed to observe the relationship between AMA and ER and explore the possible mechanisms.

The effect of Nifedipine on embryo transfer outcomes: A randomized clinical trial.

Endometrial receptivity is crucial for embryo implantation, and excessive uterine contraction reduces success. Nifedipine which is a calcium channel blocker, could decrease uterine contraction and improve pregnancy outcomes. This study aimed to assess the effect of Nifedipine before embryo transfer on the pregnancy outcome in women undergoing in vitro fertilization (IVF) in a tertiary center in Iran. 150 women who were candidates for IVF were randomly assigned into 2 groups: group 1 received 20 mg Nifedipine 30 min before embryo transfer, and group 2 received no intervention. Blood pressure of the participants was monitored every 10 min for 1 hr under the supervision of an anesthesiologist. Finally, implantation rate and chemical and clinical pregnancy rates were compared between groups. At the end of the study, 140 participants were included in the final analyses. No significant difference was observed in clinical pregnancy rates between groups (20% vs. 22%, p = 0.51). Nifedipine administration before embryo transfer does not improve the implantation and clinical pregnancy rates in women undergoing IVF.

Efficacy of In-utero Infusion of Autologous Platelet Rich Plasma Therapy in Women with Recurrent Implantation Failure: A Systematic Review and Meta-analysis of Randomised Controlled Trials

Introduction: In-utero infusion of autologous Platelet Rich Plasma (PRP) is found to be a novel approach to address the thin, non receptive endometrium leading to recurrent implantation failure. Aim: To estimate the efficacy of intrauterine PRP infusion in subfertile females affected with recurrent implantation failure via the conduction of a systematic review and meta-analysis of the available Randomised Controlled Trials (RCTs). Materials and methods: A systematic literature search was done in electronic databases like Medline (through PubMed), Embase, Scopus, Web of Science, and Cochrane database from January 2000 to November 2020 using keywords like “In-vitro Fertilisation” OR “IVF” OR “Intracytoplasmic sperm injection” OR “ICSI” OR “Embryo transfer” AND “Platelet rich plasma” OR “PRP” OR “Autologous platelet rich plasma” OR “Platelet rich plasma” and “recurrent implantation failure”. The randomised controlled trials, comparing intrauterine infusion of PRP versus no intervention or placebo in a study population of subfertile women with recurrent implantation failure and having medically confirmed pregnancy outcomes like live birth, clinical pregnancy, chemical pregnancy, and miscarriage were included in this systematic review. Studies with inadequate details in the methodology or result section were excluded from this analysis. This meta-analysis involved a pooled data analysis of 335 participants (174 cases and 161 controls) from four RCTs. Results: Compared with the control group, patients in the PRP group were found to have more beneficial effects in terms of implantation rate (Relative risks: 1.51, 95% Confidence interval: 0.94, 2.44; Heterogeneity: Tau²=0.08; I²=44%; Test for overall effect: Z=1.69, p-value=0.09) and clinical pregnancy (Relative risk: 1.88, 95% CI: 1.17, 3.03; Heterogeneity: Tau²=0.12; I²=51%; Test for overall effect: Z=2.62; p-value=0.009). Conclusion: Intrauterine PRP infusion increases the implantation rate and clinical pregnancy rate in women undergoing the frozen embryo transfer cycle.

Value of Intrauterine Injection of HCG (Human Chorionic Gonadotropin) before Fresh Embryo Transfer on Clinical Pregnancy Rate in Women with Previous Failed One or Two ICSI (Intra Cytoplasmic Sperm Injection) Trials

Value of Intrauterine Injection of HCG (Human Chorionic Gonadotropin) before Fresh Embryo Transfer on Clinical Pregnancy Rate in Women with Previous Failed One or Two ICSI (Intra Cytoplasmic Sperm Injection) Trials

Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome.

Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome.

Chronic Endometritis in Infertile Women: Impact of Untreated Disease, Plasma Cell Count and Antibiotic Therapy on IVF Outcome-A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aims to evaluate the impact of chronic endometritis (CE) and its therapy on in vitro fertilization (IVF) outcome. Additionally, we aim to investigate whether various degrees of CE severity may exert a different effect on IVF outcome. Ongoing-pregnancy rate/live-birth-rate (OPR/LBR), clinical-pregnancy rate (CPR), and miscarriage rate (MR) were calculated. A total number of 4145 patients (from ten studies) were included. Women with CE had lower OPR/LBR (OR 1.97, p = 0.02) and CPR (OR 2.28, p = 0.002) compared to those without CE. CE cure increased OPR/LBR (OR 5.33, p < 0.0001) and CPR (OR 3.64, p = 0.0001). IVF outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR and MR: p = ns). Women with severe CE had lower OPR/LBR (OR 0.43, p = 0.003) and CPR (OR 0.40, p = 0.0007) compared to those mild CE. Mild CE showed no influence on the IVF outcome as compared to women without CE (OPR/LBR, CPR and MR: p = ns). Based on this data analysis, CE significantly reduces OPR/LBR and CPR in women undergoing IVF. Importantly, CE resolution after antibiotic therapy may improves IVF outcome, leading to similar OPR/LBR and CPR as compared to unaffected patients. The negative effects of CE on IVF outcome may be restricted to severe disease, whereas mild CE may have no influence on IVF success.

Transcutaneous electrical acupoint stimulation improves endometrial receptivity resulting in improved IVF-ET pregnancy outcomes in older women: a multicenter, randomized, controlled clinical trial

ObjectiveTo examine the effects and mechanisms of transcutaneous electrical acupoint stimulation (TEAS) on pregnancy outcomes in women undergoing in vitro fertilization (IVF)-embryo transfer (ET).Design, setting, and participantsThis efficacy study was a multicenter, randomized, controlled clinical trial (RCT) in women receiving IVF-ET. The mechanistic study was a single-center RCT.InterventionsThe participants received TEAS vs. no TEAS treatment.Main outcome measuresIn the efficacy study, the primary outcomes were the rates of clinical pregnancy, embryo implantation, and live birth. In the mechanistic study, sex hormones and endometrial protein expression were examined.ResultsUltimately, 739 participants were enrolled (367 and 372 in the TEAS and control groups, respectively). The clinical pregnancy rate was higher in the TEAS group than in the controls (55.1% vs. 46.7%, P = 0.03). There were no significant differences in embryo implantation, biochemical pregnancy, and live birth rates between the two groups (all P > 0.05) in the study population. In women > 35 years, the clinical pregnancy rates, embryo implantation rates and live birth rates in the TEAS and control groups were 48.9% vs. 23.7% (P = 0.004),30.8 vs. 13.9% (P = 0.001) and 34.0% vs. 19.7% (P = 0.06) respectively. In the mechanistic study with 120 participants, on the theoretical embryo implantation day, better developed endometrial pinopodes, elevated endometrial integrin α1β1/αVβ3, leukemia inhibitory factor, and elevated serum progesterone levels were found in the TEAS group compared with controls.ConclusionTEAS significantly improved the clinical pregnancy rate in women undergoing IVF-ET, especially in women of older age. It might be due to improved endometrial receptivity.Trial registrationChiCTR-TRC-13003950.

Effect of vaginal/oral tadalafil on endometrial thickness in IVF patients: a double-blind, placebo controlled RCT: a pilot study.

To investigate the effect of tadalafil (a long working phosphodiesterase type 5 inhibitor) on the endometrial thickness, biochemical pregnancy rates and clinical pregnancy rates in women in an in vitro fertilization treatment. This study investigates the use of vaginal and oral administration of tadalafil. This is a prospective double-blind placebo-controlled randomized controlled trial with 58 patients in an in vitro fertilization treatment with a short antagonist stimulation protocol. The study population is divided into three equal groups comparing oral and vaginal administration of tadalafil to a control group. No significant difference in endometrial thickness and number of biochemical and clinical pregnancies was found between the three groups. This study could not show a significant benefit of administration of tadalafil. However, a trend towards more pregnancies in the group treated with oral tadalafil is seen, more research in specific subgroups is needed.