Search Results (31)

Background/Objectives: GnRH agonists may offer potential benefits when used for luteal phase support in assisted reproductive treatments. This systematic review and meta-analysis of randomized controlled trials evaluates the effect of a single-dose administration of gonadotropin-releasing hormone (GnRH) agonist on the day of frozen-thawed embryo transfer (FET) in artificial cycles, in terms of reproductive outcomes. Methods: A comprehensive literature search was performed using the PubMed and Cochrane databases to identify relevant studies. The outcomes assessed were live birth rate, clinical pregnancy rate, positive pregnancy test, implantation rate, and miscarriage rate. Three randomized controlled trials were included in the analysis. Results: The clinical pregnancy rate (56.5% vs. 47.4%; OR 1.27; 95% CI: 1.01–1.60; p = 0.0426) and live birth rate (34.3% vs. 23.9%; OR 1.71; 95% CI: 1.00–2.91; p = 0.0483) were significantly higher in the treatment group compared to the control group. No statistically significant differences were observed between the groups in terms of positive pregnancy test, implantation rate, or miscarriage rate, although the analysis revealed a trend toward improved outcomes in the intervention group. Conclusions: In summary, although our meta-analysis indicates that a single dose of GnRH agonist in artificial FET cycles may be associated with improved clinical pregnancy and live birth rates, these findings are based on a limited number of available trials. Larger, well-designed randomized controlled trials are urgently needed before any changes to clinical recommendations can be justified. Full article

Background/Objectives: Until recently, oral dydrogesterone has only been established in fresh in vitro fertilization (IVF) cycles, whereas its role in luteal phase support (LPS) for frozen embryo transfer (FET) cycles remains unclear. The aim of this study is to determine whether oral dydrogesterone as LPS in FET cycles results in pregnancy rates comparable to vaginal progesterone, focusing primarily on ongoing pregnancy rates, but also on clinical pregnancy, miscarriage, and live birth rates. Methods: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Five databases (Embase, MEDLINE^®, APA PsycInfo, Global Health, and HMIC) and two additional sources were searched from inception to November 28, 2024. Only randomized controlled trials (RCTs) were included. A common effects model combined risk estimates, and heterogeneity was assessed using I². Study quality was evaluated with Risk of Bias 2 (RoB2), and evidence certainty was graded using GRADE. Results: Overall, five RCTs with a total of 636 women were included in the meta-analysis. The comparison between oral dydrogesterone and vaginal progesterone for LPS did not yield significant differences for any of the outcomes studied. For ongoing pregnancies, the pooled odds ratio (OR) was 0.90 (95% CI: 0.59–1.35), with no heterogeneity (I² = 8.7%). For miscarriage events, the OR was 1.41 (95% CI: 0.63–3.13, I² = 0). For clinical pregnancies, the OR was 0.94 (95% CI: 0.62–1.42, I² = 49.2%), with heterogeneity attributed to dosage. For live births, the pooled OR was 1.08 (95% CI: 0.67–1.75, I² = 0%). Two studies were assessed as high risk of bias, two as low risk, and one as moderate. The GRADE assessment indicated low to moderate certainty of evidence. Conclusions: Oral dydrogesterone and vaginal progesterone yield comparable reproductive outcomes for LPS in FET cycles. Given its ease of administration, dydrogesterone may serve as a viable alternative in future FET protocols. However, further RCTs are needed to assess its efficacy against other progesterone administration routes. Full article

Background/Objectives: Infertility affects couples at reproductive age, with in vitro fertilization (IVF) being the most effective treatment. Success rates of IVF are influenced by several factors, including a healthy female reproductive system microbiome, which can improve implantation rates and pregnancy outcomes. This study evaluated the impact of Ligilactobacillus salivarius PS11610 on IVF outcomes. This strain showed antimicrobial activity against pathogens related to dysbiosis, commonly observed in women undergoing assisted reproductive treatment. Results: The administration of L. salivarius PS11610 at a dose of 1 × 10⁹ CFU every 12 h for at least one month before IVF procedures, particularly in the frozen embryo transfer (FET) group, appears to enhance the success rate of IVF. IVF procedures without embryo transfer showed no significant differences between the groups. However, there were statistically significant differences in the quality of embryos, specifically in category 2, which were higher in the group without L. salivarius PS11610 supplementation (p = 0.042). Similar results were seen in the IVF with embryo transfer group, where the quality of embryos in categories 2 and 3 was higher in the group without L. salivarius PS11610 (p = 0.019 and p = 0.05, respectively). IVF with FET showed notable improvements, where intake of L. salivarius PS11610 was associated with a significant increase in live birth infants (26.4% with L. salivarius PS11610 vs. 17.9% without, p = 0.034) and higher biochemical pregnancy rates (42.6% vs. 34%, p = 0.071). Conclusions: Despite some differences in embryo quality, the overall positive impact on pregnancy and birth outcomes highlights L. salivarius PS11610 as a promising supplement in assisted reproductive treatments. Full article

Background: In frozen embryo transfer (FET) cycles, optimal endometrial thickness on ovulation day is typically 7–8 mm before progesterone administration. Recent studies have highlighted the significant inverse correlation between ongoing pregnancy rates and changes in endometrial thickness during the secretory phase after progesterone exposure, particularly by the day of embryo transfer (ET). This study aims to investigate how changes in endometrial thickness from the end of the proliferative phase to ET impact FET outcomes. Methods: We conducted a prospective observational cohort study involving 247 FET cycles, divided into hormonally based (102) and ovulatory-based (145) groups. Patients were monitored through transvaginal ultrasound (TVS) and blood tests. On ET day, we assessed endometrial thickness and changes compared to the last day of the proliferative phase, defining endometrial compaction as a decrease in thickness. We analyzed data to identify factors predicting cycle outcomes. Results: The study reported chemical and clinical pregnancy rates of 47.4% and 38.1%, respectively. Endometrial compaction was observed in 37.2% (92/247) of cycles, with corresponding rates of 48.9%, 32.6%, and 29.5% for chemical, clinical, and ongoing pregnancies, compared to 46.4%, 41.3%, and 28.9% in cycles without compaction. These differences were not statistically significant, and patterns of endometrial thickness change were similar across different FET protocols and progesterone exposure durations. Conclusions: The main factors influencing cycle outcomes were maternal age, embryo transfer protocol, and endometrial thickness on ET day, with endometrial compaction showing no correlation with improved outcomes. Full article

Background and Objectives: Although considerable research has been devoted to examining the distinctions between fresh and frozen embryo transfer regarding obstetric outcomes and rates of pregnancy success, there is still a scarcity of thorough analyses that specifically examine neonatal outcomes. The objective of our study was to provide an in-depth analysis of neonatal outcomes that occur after the transfer of fresh and frozen embryos (ET vs. FET) in IVF/ICSI cycles. Materials and Methods: Multiple databases (PubMed/MEDLINE, Cochrane Library, Web of Science, Wiley, Scopus, Ovid and Science Direct) were searched from January 1980 to February 2024. Two reviewers conducted the article identification and data extraction, meeting inclusion and exclusion criteria. The methodological quality was evaluated using the Newcastle–Ottawa Scale (NOS) or the revised Cochrane Risk of Bias Tool. The meta-analysis was performed using RevMan 5.4. Results: Twenty studies, including 171,481 participants in total, were subjected to qualitative and quantitative analyses. A significant increase in preterm birth rates was noted with fresh embryo transfer compared to FET in the overall IVF/ICSI population (OR 1.26, 95% CI 1.18–1.35, p < 0.00001), as well as greater odds of a low birth weight (OR 1.37, 95% CI 1.27–1.48, p < 0.00001) and small-for-gestational-age infants in this group (OR 1.81, 95% CI 1.63–2.00, p < 0.00001). In contrast, frozen embryo transfer can result in macrosomic (OR 0.59, 95% CI 0.54–0.65, p < 0.00001) or large-for-gestational-age infants (OR 0.64, 95% CI 0.60–0.69, p < 0.00001). No significant difference was observed regarding congenital malformations or neonatal death rates. Conclusions: This systematic review confirmed that singleton babies conceived by frozen embryo transfer are at lower risk of preterm delivery, low birthweight and being small for gestational age than their counterparts conceived by fresh embryo transfer. The data support embryo cryopreservation but suggest that elective freezing should be limited to cases with a proven indication or within the framework of a clinical study. Full article

Essential trace elements are micronutrients whose deficiency has been associated with altered fertility and/or adverse pregnancy outcomes, while surplus may be toxic. The concentrations of eight essential trace elements were measured using inductively coupled mass spectrometry (ICP-MS) and assessed with respect to clinical in vitro fertilization (IVF) outcomes in a population of 51 women undergoing IVF with intracytoplasmic sperm injection (ICSI), pre-implantation genetic screening for aneuploidy (PGT-A), and single frozen euploid embryo transfer (SET/FET). Specifically, copper (Cu), zinc (Zn), molybdenum, selenium, lithium, iron, chromium, and manganese were quantified in follicular fluid and whole blood collected the day of vaginal oocyte retrieval (VOR) and in urine collected the day of VOR and embryo transfer. We found that the whole blood Cu/Zn ratio was significantly associated with superior responses to ovarian stimulation. Conversely, the whole blood zinc and selenium concentrations were significantly associated with poor ovarian response outcomes. Higher levels of whole blood zinc and selenium, urinary selenium, lithium, and iron had significant negative associations with embryologic outcomes following IVF. Regarding clinical IVF outcomes, higher urinary molybdenum concentrations the day of VOR were associated with significantly lower odds of implantation and live birth, while higher urinary Cu/Mo ratios on the day of VOR were associated with significantly higher odds of implantation, clinical pregnancy, and live birth. Our results suggest that essential trace element levels may directly influence the IVF outcomes of Spanish patients, with selenium and molybdenum exerting negative effects and copper-related ratios exerting positive effects. Additional studies are warranted to confirm these relationships in other human populations. Full article

Objectives: To evaluate the effect of intrauterine infusion and hysteroscopic injection of autologous platelet-rich plasma (PRP) in patients with a persistent thin endometrium (EM) undergoing euploid frozen embryo transfer (EFET) cycles. Methods: This prospective case–control study enrolled 116 infertile women with thin EM (<7 mm) who underwent hormone replacement therapy (HRT) for EFET. These women had experienced at least one previous unsuccessful EFET cycle, which either resulted in the cancellation of the cycle or failure of pregnancy. A total of 55 women received an intrauterine infusion of PRP before FET, 38 received a hysteroscopic injection of PRP, and 23 received standard HRT treatment without PRP (control group). Only euploid embryos were transferred in these cycles. The primary outcomes were the implantation rate (IR) and clinical pregnancy rate (CPR) after EFET. Results: After receiving intrauterine infusion and hysteroscopic injection of PRP, 78.2% and 55.3% of patients, respectively, showed an EM thickness exceeding 7 mm, followed by embryo transfer. The hysteroscopic injection group demonstrated significantly higher IR (52%), a higher trend of CPR (52%), and a higher live birth rate (38%) than the control group (18%, 22%, and 4%). Conclusions: Intrauterine infusion and hysteroscopic injection of autologous PRP may be effective methods to increase EM thickness in HRT cycles. According to our results, both methods could increase EM thickness, while hysteroscopic injection appeared to provide more significant assistance in increasing IR, CPR, and live birth rate after EFET in patients with persistent thin EM. Full article

This study investigates the effect of GnRHa pretreatment on pregnancy outcomes in artificial endometrial preparation for frozen–thawed embryo transfer (AC-FET) cycles. A systematic review of English language studies published before 1 September 2022, was conducted, excluding conference papers and preprints. Forty-one studies involving 43,021 participants were analyzed using meta-analysis, with a sensitivity analysis ensuring result robustness. The study found that GnRHa pretreatment generally improved the clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR). However, discrepancies existed between randomized controlled trials (RCTs) and observational studies; RCTs showed no significant differences in outcomes for GnRHa-treated cycles. Depot GnRHa protocols outperformed daily regimens in LBR. Extended GnRHa pretreatment (two to five cycles) significantly improved CPR and IR compared to shorter treatment. Women with polycystic ovary syndrome (PCOS) saw substantial benefits from GnRHa pretreatment, including improved CPR and LBR and reduced miscarriage rates. In contrast, no significant benefits were observed in women with regular menstruation. More rigorous research is needed to solidify these findings. Full article

Despite serum progesterone being a widely accepted method for luteal phase support during embryo transfer cycles, debates persist regarding the optimal strategy for guiding clinical decisions on progesterone dosages to maximize reproductive outcomes. This retrospective study explored the utility of microRNA (miRNA) biomarkers in guiding personalized progesterone dosage adjustments for frozen embryo transfer (FET) cycles in 22 in vitro fertilization (IVF) patients undergoing hormone replacement therapy. Utilizing MIRA, an miRNA-based endometrial receptivity test, we analyzed patients’ miRNA expression profiles before and after progesterone dosage adjustments to determine suitable dosages and assess endometrial status. Despite patients receiving identical progesterone dosages, variations in miRNA profiles were observed in the initial cycle, and all patients presented a displaced window of implantation. Following dosage adjustments based on their miRNA profiles, 91% of patients successfully transitioned their endometrium towards the receptive stages. However, two patients continued to exhibit persistent displaced receptivity despite the adjustments. Given the evident variation in endometrial status and serum progesterone levels among individuals, analyzing miRNA expression profiles may address the challenge of inter-personal variation in serum progesterone levels, to deliver more personalized dosage adjustments and facilitate personalized luteal phase support in IVF. Full article

Background and Objective: The aim of this retrospective cohort study is to evaluate the impact of assisted reproductive treatment (ART) on adverse maternal outcomes and the rate of hospitalization in maternal intensive care (MIC) in a tertiary university center in Liege, Belgium. Materials and Methods: This is a retrospective cohort study comparing two groups, 6557 patients who achieved pregnancy spontaneously and 330 patients who achieved pregnancy after ART, between January 2020 and December 2022. These patients were followed in the academic obstetrics department of Citadelle Hospital, Liège. The database of the ART center was compared with the database of the delivery unit to determine the cohort of patients who conceived after ART. Adverse maternal outcomes and MIC hospitalization rates were compared with between spontaneous pregnancies and ART groups. ART groups were also compared with each other. Results: The rate of hospitalization in maternal intensive care for patients who achieved pregnancy spontaneously was 12.1%, compared to 17.3% after ART. Comparing the rate of pre-eclampsia, 3.5% of spontaneous pregnancies were complicated by pre-eclampsia, while after ART, 10.9% of patients developed this complication during pregnancy. This rate was higher after IVF (12%) compared to intrauterine insemination and particularly after frozen embryo transfer (FET) in artificial cycle (17.9%). The birthweight of newborns after ART was also analyzed. A significant difference was obtained when comparing fresh embryo transfer with FET. Conclusions: Our study confirmed that FET in artificial cycle is a risk factor for pre-eclampsia and that fresh embryo transfer is associated with a higher rate of newborns with a lower percentile of birthweight. Our data showed that the rate of MIC hospitalization was significantly higher after ART but did not differ between groups. Full article

Optimizing endometrial thickness (EMT) is crucial for successful embryo implantation, but enhancing thin endometrium remains a significant challenge. Platelet-rich plasma (PRP)-derived therapies have emerged as a promising approach in reproductive medicine due to their capacity to facilitate tissue repair and regeneration. This study aims to identify the risk factors associated with the failure of intrauterine PRP infusion for thin endometrium in women with recurrent implantation failure (RIF). We retrospectively reviewed data from 77 women with RIF, all exhibiting an EMT of <7 mm. These women underwent programmed hormone therapy for frozen embryo transfer (FET) and received two autologous intrauterine PRP infusions. Following intrauterine PRP-lysate (PL) infusions, the mean increase in EMT was 1.9 ± 1.2 mm, with EMT reaching 7 mm in 86% of the cases (66/77; average EMT, 8.3 mm). We identified an exceedingly thin EMT as a risk factor impacting the therapeutic efficacy in increasing EMT (p = 0.04, OR: 3.16; 95% CI: 1.03–9.67). Additionally, the number of previous uterine surgeries emerged as a prognostic factor for pregnancy failure following PL infusion (p = 0.02, OR: 2.02; 95% CI: 1.12–3.64). Our findings suggest that an extremely thin EMT and a history of numerous uterine surgeries can impede successful pregnancy, even when an optimal EMT is achieved following PRP infusion. Full article

(1) Background: The presence of adenomyosis among pregnant patients has been associated with a higher incidence of miscarriage and pregnancy complications. Although the role of adenomyosis in women undergoing in vitro fertilization (IVF) was investigated in several studies and demonstrated a potentially detrimental effect on live birth rates following IVF, most of them were small studies in which the adenomyosis diagnosis was not confirmed based on solid ultrasonographic criteria. (2) Methods: 3503 patients undergoing their first blastocyst frozen transfer through a hormonal replacement (HRT) FET cycle. Among them, 140 women had a confirmed diagnosis of adenomyosis based on the MUSA criteria. (3) Results: Adenomyosis patients were more likely to proceed with deferred FET compared with no-adenomyosis women (p = 0.002) and were significantly more likely to be treated with GnRH agonist pre-treatment (2 months) (p < 0.001). The presence of adenomyosis significantly decreased the clinical pregnancy rates (aOR 0.62, 95% CI: 0.39–0.98, p = 0.040) and live birth rates (aOR 0.46, 95% CI: 0.27–0.75, p = 0.003) and significantly increased the miscarriage rates (aOR 2.13, 95% CI: 0.98–4.37, p = 0.045). Multivariable logistic regression adjusting for age, autologous or donor oocytes, PGT-A, deferred FET, serum progesterone levels the day before FET, GnRH agonist pre-treatment, number of embryos transferred, and adenomyosis demonstrated that the use of the GnRH agonist protocol did not decrease or increase the miscarriage rate, clinical pregnancy rate, or live birth rate. (4) Conclusions: The presence of adenomyosis had a significant negative impact on the clinical outcomes of patients undergoing FET and was associated with higher miscarriage, lower clinical pregnancy, and live birth rates. GnRH agonist pre-treatment does not appear to improve clinical outcomes. Full article

This study aims to determine the association of non-essential trace elements present in follicular fluid, plasma, and urine with reproductive outcomes of women undergoing intracytoplasmic sperm injection (ICSI), preimplantation genetic testing for aneuploidies (PGT-A) and single frozen euploid embryo transfer (SET/FET). This single-center, prospective cohort study included sixty women undergoing ICSI with PGT-A and SET/FET between 2018 and 2019. Urine, plasma and follicular fluid samples were collected on the vaginal oocyte retrieval day to simultaneously quantify ten non-essential trace elements (i.e., Ba, Sr, Rb, Sn, Ti, Pb, Cd, Hg, Sb, and As). We found several associations between the levels of these non-essential trace elements and clinical IVF parameters. Specifically, the increased levels of barium in follicular fluid were negatively associated with ovarian function, pre-implantation development and embryo euploidy, while elevated strontium concentrations in this biofluid were negatively associated with impaired blastulation and embryo euploidy. Elevated plasma strontium levels were negatively associated with ovarian function, fertilization and blastulation. Enhanced presence of other trace elements in plasma (i.e., rubidium and arsenic) were associated with a diminished ovarian function and limited the number of recovered oocytes, mature oocytes and zygotes, respectively. Fully adjusted models suggested significantly lower odds of achieving a live birth when increased concentrations of barium and tin were found in urine. Full article

The impact and safety of phytoestrogens, plant-derived isoflavones with estrogenic activity predominantly present in soy, on female reproductive health and IVF outcomes continues to be hotly debated. In this prospective cohort study, 60 women attending IVI-RMA New Jersey undergoing IVF with single frozen embryo transfer (SET/FET) of good-quality euploid blastocyst after PGT-A analysis were recruited. Concentrations of two phytoestrogens (daidzein and genistein) in follicular fluid (FF) and urine (U) were measured by UPLC–MSMS, both collected on vaginal oocyte retrieval day. These measurements correlated with IVF clinical outcomes. In models adjusted for age, BMI, race/ethnicity, and smoking status, higher FF phytoestrogen concentrations were significantly associated with higher serum estradiol, enhanced probability of implantation, clinical pregnancy, and live birth. Moreover, higher urine phytoestrogen concentrations were significantly associated with improved oocyte maturation and fertilization potential and increased probability of clinical pregnancy and live birth. Finally, higher FF and urine phytoestrogen concentrations were associated with a higher probability of live birth from a given IVF cycle. Our results suggest that dietary phytoestrogens improved reproductive outcomes of women undergoing IVF treatment. However, additional prospective studies are needed to optimize the use of phytoestrogens to further enhance reproductive outcomes and/or protect against reproductive insults. Full article

Background: The proportion of frozen embryo transfer cycles has consistently grown in recent decades. Some adverse obstetric outcomes after frozen embryo transfer could possibly be explained by different approaches in endometrial preparation. The aim of the present study was to investigate reproductive and obstetric outcomes after frozen embryo transfer, comparing different endometrial preparation strategies. Methods: This retrospective study included 317 frozen embryo transfer cycles, of which 239 had a natural or modified natural cycle and 78 underwent artificial endometrial preparation. After excluding late abortion and twin pregnancies, the outcomes of 103 pregnancies were analyzed, 75 of which were achieved after a natural cycle/modified natural cycle, and 28 were achieved after an artificial cycle. Results: The overall clinical pregnancy rate/embryo transfer was 39.7%, the miscarriage rate was 10.1%, and the live birth rate/embryo transfer was 32.8%, without significant differences in reproductive outcomes between natural/modified cycle and artificial cycle groups. The risks of pregnancy-induced hypertension and abnormal placental insertion were significantly increased in pregnancies achieved after the artificial preparation of the endometrium (p = 0.0327 and =0.0191, respectively). Conclusions: Our study encourages the use of a natural cycle or modified natural cycle for endometrial preparation for frozen embryo transfer in order to ensure the presence of a corpus luteum able to orchestrate maternal adaptation to pregnancy. Full article