Search Results (32)

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, with ovulation induction remaining the first-line treatment approach. Although letrozole has emerged as the most effective monotherapy, treatment resistance, side effects, and patient preferences have led to increasing interest in adjunctive or alternative approaches. This narrative review summarizes the current evidence for ovulation induction in patients with PCOS, including conventional pharmacologic agents, such as clomiphene citrate, letrozole, gonadotropins, and insulin-sensitizing agents, as well as complementary therapies, such as acupuncture and Chinese herbal medicine. We also examine emerging adjuvants, such as vitamin D, omega-3 fatty acids, sildenafil, and antioxidants that may enhance clinical pregnancy rates or improve endometrial receptivity. While robust evidence supports the use of letrozole as a first-line agent, complementary and integrative therapies may offer additional benefits, particularly in treatment-resistant or preference-driven contexts. Further high-quality studies are needed to clarify the role of combined therapeutic strategies in optimizing fertility outcomes for women with PCOS. Full article

Letrozole, a third-generation aromatase inhibitor initially developed for breast cancer, has become the preferred first-line agent for ovulation induction (OI), particularly in women with polycystic ovary syndrome (PCOS). This narrative review critically evaluates the efficacy, safety, and clinical applications of letrozole across diverse infertility contexts. Compared to clomiphene citrate, letrozole is associated with higher ovulation and live birth rates, a lower risk of multiple gestation, and a more favorable endometrial environment. Its pharmacokinetics—marked by transient estrogen suppression and a short half-life—limit embryonic exposure, supporting its favorable safety profile. Emerging data from large, randomized trials and meta-analyses demonstrate no increase in congenital anomalies, miscarriage, or adverse perinatal outcomes in letrozole-conceived pregnancies. Moreover, maternal side effects are generally mild, and the risk of ovarian hyperstimulation syndrome is low. Letrozole has also shown utility in mild stimulation protocols, fertility preservation for estrogen-sensitive malignancies, and clomiphene-resistant PCOS. Key clinical strategies—such as early-cycle initiation, lowest effective dosing, and individualized monitoring—optimize therapeutic outcomes while minimizing potential risks. While long-term offspring data remain limited and mechanistic concerns persist, current evidence robustly supports letrozole as a safe and effective option for OI, balancing reproductive success with maternal–fetal safety across a range of infertility indications. Full article

Background: Infertility affects 8–12% of couples globally, with causes including hormonal and structural abnormalities. Letrozole, an aromatase inhibitor, is commonly used for ovulation induction, but its role in various assisted reproductive technologies (ARTs) and across different subgroups of infertile women remains unclear. Objective: This scoping review aimed to map the existing evidence on the use of letrozole in assisted reproductive cycles, focusing on reproductive outcomes and its application across different patient populations. Methods: A scoping review was conducted following the PRISMA-ScR guidelines. Twelve studies—including randomized controlled trials and retrospective cohorts—were identified through a structured search strategy. Studies comparing letrozole alone or in combination with gonadotropins/clomiphene to other stimulation protocols were included. Data were charted across multiple outcomes including oocyte yield, implantation, pregnancy, miscarriage, and live birth rates. Results: Evidence suggests that letrozole-based protocols may enhance oocyte yield and improve reproductive outcomes in certain settings. The highest implantation rate (57%) was observed in natural cycles, while the letrozole-only group showed the highest clinical pregnancy (50.57%) and live birth rates (45.58%). Combination protocols achieved the highest ongoing pregnancy rate (58.3%), with the lowest miscarriage rate (14.86%) in the letrozole-only group. Conclusions: Letrozole appears to be a versatile agent in ART, especially for patients requiring reduced gonadotropin doses or estradiol modulation. This scoping review highlights the need for further research to clarify its optimal use across different infertility subgroups and ART modalities. Full article

Background and Objectives: Pregnancies resulting from assisted reproductive technology (ART) have been associated with placenta-related adverse outcomes. Uterine artery Doppler pulsatility index (UtA-PI) reflects placental function. This study aimed to examine whether second-trimester UtA-PI differs according to the conception method after adjusting for potential confounding factors. Materials and Methods: In this retrospective cohort study, we included data from February 2015 to August 2024, at the third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, on singleton pregnancies presenting for their routine antenatal care, including a second-trimester anomaly scan. Pregnancies conceived via ART, including those conceived via ovulation induction/intrauterine insemination (OI/IUI) or in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), were compared to those conceived spontaneously. Multiple linear regression was employed to investigate the association between the mode of conception and log₁₀ UtA-PI values, adjusting for various confounders, including gestational age at the time of the scan, maternal weight, height, age, parity, mode of delivery, smoking status, pre-existing diabetes mellitus (type I or II), and pre-existing thyroid disease. Results: The study included 15,552 singleton pregnancies, of which 82 (0.5%) were conceived via OI/IUI and 690 (4.4%) were conceived via IVF/ICSI. The median UtA-PI values were 0.99 (IQR: 0.85–1.17) for spontaneous conception (SC), 1.00 (IQR: 0.86–1.16) for OI/IUI, and 0.90 (IQR: 0.76–1.12) for IVF/ICSI. The Kruskal–Wallis test indicated a statistically significant difference among these groups (p < 0.001). Pairwise comparisons using the Wilcoxon rank-sum test with Bonferroni correction revealed that UtA-PI values in IVF/ICSI pregnancies were significantly lower compared to both SC and OI/IUI pregnancies (p < 0.001 for both). No significant difference was observed between the SC and OI/IUI groups. In the multivariable linear regression model, IVF/ICSI conception was independently associated with lower log₁₀ UtA-PI values (estimate = −0.076, 95% CI: −0.096, −0.056) while no association was found for OI/IUI conception. Conclusions: Although ART has been associated with placental-related complications, mid-trimester UtA flow was found to be lower in IVF/ICSI pregnancies, suggesting better utero-placental flow in ART pregnancies and other possible mechanisms in the maternal–placental interplay for the development of pregnancy complications. Full article

This retrospective cross-sectional study investigates determinants on follicular development, oocyte retrieval and pregnancy outcome. It assessed the clinical practicability of monitoring parameters in relation to predict a successful treatment. Analysis of serum-estradiol (E2), sonographic follicle count, number of oocytes and optimizable parameters have therefore been carried out based on patient files from the IVF outpatient clinic at the Department of Gynecology, Obstetrics and Reproductive Medicine, Homburg/Saar, Germany. Equidirectional connection occurred between serum-E2, sonographic follicle count and number of oocytes (p < 0.001). There was no significant difference between sonographic and punctured follicle count (p = 0.428), but between sonographic/punctured follicle count and number of oocytes obtained (p < 0.01). Increasing endometrial thickness was associated with increasing serum-E2 (p = 0.003) and number of oocytes (p < 0.001), but not with the follicle count (p > 0.05). Additionally, age was inversely associated with sonographic follicle count and number of oocytes (p < 0.001) but not with E2 (p > 0.05). BMI, nicotine and stimulation protocol had no association with the observed parameters (p > 0.05). Mean differences in follicle numbers can be used for predicting expectable numbers of oocytes. Due to comparable numbers of follicles visualized on the day of ovulation induction and the number of follicles punctured, more emphasis should be placed in optimizing oocyte retrieval procedures. Full article

Polycystic ovary syndrome is a common endocrine disorder, characterized by hyperandrogenism and/or chronic oligo/anovulation, which leads to infertility. The aim of this systematic review and meta-analysis was to explore the efficacy of letrozole compared with clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome. The study protocol has been registered with PROSPERO (registration number CRD42022376611). The literature search included randomized clinical trials. We conducted our systematic literature search across three medical databases: MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. The data synthesis employed a random effects model. Out of the 1994 articles screened, 25 studies fulfilled the inclusion criteria. The letrozole group exhibited a significant increase in endometrial thickness (mean difference = 1.70, confidence interval: 0.55–2.86; I² = 97%, p-value = 0.008). The odds of ovulation (odds ratio = 1.8, confidence interval: 1.21–2.69; I² = 51%, p-value = 0.010) and pregnancy (odds ratio = 1.96, confidence interval: 1.37–2.81; I² = 32%, p-value = 0.002) were significantly higher. The resistance index of the subendometrial arteries showed a significant decrease (mean difference = −0.15, confidence interval: −0.27 to −0.04; I² = 92%, p-value = 0.030). Women diagnosed with polycystic ovarian syndrome and treated with letrozole for ovulation induction had increased ovulation and pregnancy rates and increased endometrial thickness. The lower resistance index of subendometrial arteries can enhance intrauterine circulation, creating more favorable conditions for embryo implantation and development. Full article

The administration of GnRH and its agonists benefits various aspects of bovine reproductive programs, encompassing physiological stages such as estrous synchronization, post-insemination, pregnancy, and the postpartum period. The positive impact of GnRH administration in overcoming challenges like repeat breeder cows, early embryonic loss prevention, and the management of cystic ovarian disease (COD) is thoroughly surveyed. Furthermore, this review focuses on the significance of GnRH administration during the postpartum period, its role in ovulation induction, and how it enhances the productivity of embryo transfer (ET) programs. An emerging feature of this field is introduced, focusing on nano-drug delivery systems for GnRH agonists, and the potential benefits that may arise from such advancements are highlighted. While this review offers valuable insights into various applications of GnRH in bovine reproduction, it emphasizes the crucial need for further research and development in this field to advance reproductive efficiency and health management in dairy cattle. Full article

We investigated the effects of short-term glycerin supplementation on follicular dynamics and pregnancy rates. Twenty-five goats with synchronized estrus and follicular waves with three injections of a prostaglandin analog every 7 days were used. Two days after the second injection, 13 goats were randomly chosen to receive an oral drench of 200 mL of glycerin (glycerin group [GG], n = 13) for 6 days, whereas the remaining 12 animals received an oral drench of saline (control group [CG], n = 12). At 24 and 48 h after the third injection, the goats mated. The animals were kept in a collective stall and received the same diet. The GG had higher blood glucose levels during the supplementation period than the CG (76.4 ± 1.9 vs. 50.3 ± 0.7 mg/dL; p < 0.01). The glycemic peak was recorded 4 h after the glycerin administration (102.3 ± 5.1 mg/dL) and remained higher than that in the CG 8 and 12 h later. The GG goats had a higher rectal temperature, heart rate, and respiratory rate than the CG goats and showed an increase in these parameters 4, 8, and 12 h after glycerin drenching. The GG animals also exhibited increased stress, urination, and drinking behaviors and reduced rumination. The ultrasonographic analysis showed a higher number of follicles with a diameter >4 mm (p < 0.05) and a greater follicular diameter (p < 0.01) in the waves before and after ovulation induction. The pregnancy and twinning rates and litter size at parturition were not different between the groups. Short-term supplementation with glycerin positively affects ovarian stimulation but has no effect on the reproductive response after mating. Full article

Based on a circular economy approach, we evaluated the possible effect of targeted supplementation with leftover feed from dairy cows (i.e., intensive system) on the reproductive performance of crossbred/rangeland goats (i.e., extensive system) in arid Northern Mexico. During the deep-anestrous season (i.e., March–April, 25° North), multiparous goats (n = 38) with a similar body weight (BW) and body condition score (BCS) were randomly assigned to two groups: (1) supplemented group (SG; n = 19; BCS: 1.76 ± 0.07; BW: 43.7 ± 1.8 kg), receiving 400 g goat d⁻¹ of dairy-cow-feed leftovers prior to grazing; and (2) non-supplemented group (NS; n = 19; BCS: 1.76 ± 0.06; BW: 44.3 ± 2.5 kg). Both groups were directed to the rangeland for a period of ≈8 h. While the experimental period lasted 36 d, the experimental breeding considered 11 d (d0–d10). The anovulatory status of goats was ultrasonographically confirmed on days −20, −10, and −1 prior to male–female interaction. Previously, bucks were separated for 3 weeks from the experimental females and received exogenous testosterone every third day (i.e., 50 mg i.m.) prior to mating. With respect to the response variables, namely BW, BCS, blood glucose levels (BGLs), estrus induction (GIE, %), latency to estrus (LTE, h), estrus duration (ED, h), and luteal tissue volume (LTV, mm), no differences (p > 0.05) occurred between experimental groups. However, the response variables, namely goats ovulating (GO, %; 78.9 vs. 47.3), total number of corpuses luteum (TNCL, n; 27 vs. 13), ovulation rate (OR, n; 1.42 vs. 0.73), multiple ovulation (MO, %; 73.3 vs. 55.5), and pregnancy rate on d 36 (PRd36, %, 68.4 vs. 36.8), favored (p < 0.05) the SG over the NS goats. Our results demonstrate that connecting the circularity of two divergent ruminant production systems (i.e., cow-intensive and goat-extensive) by using dairy cows’ feed leftovers as a targeted supplementation strategy in anestrous goats under a marginal-rangeland production system enhanced out-of-season reproductive outcomes (i.e., ovulation rate and pregnancy rate), thus benefiting marginal goat producers and their families. Full article

Background: Controversy exists in the literature regarding the possible association between infertility treatments in singleton pregnancies and long-term risk for childhood malignancy. Data regarding infertility treatments in twins and long-term childhood malignancies are scarce. Objective: We sought to investigate whether twins conceived following infertility treatments are at an increased risk for childhood malignancy. Study design: A population-based retrospective cohort study, comparing the risk for future childhood malignancy in twins conceived by infertility treatments (in vitro fertilization and ovulation induction) and those who were conceived spontaneously. Deliveries occurred between the years 1991 and 2021 in a tertiary medical center. A Kaplan–Meier survival curve was used to compare the cumulative incidence of childhood malignancies, and a Cox proportional hazards model was constructed to control for confounders. Results: During the study period, 11,986 twins met the inclusion criteria; 2910 (24.3%) were born following infertility treatments. No statistically significant differences were noted between the groups comparing the rate (per 1000) of childhood malignancies (2.0 in the infertility treatments group vs. 2.2 in the comparison group, OR 1.04, 95% CI 0.41–2.62; p = 0.93). Likewise, the cumulative incidence over time was comparable between the groups (log-rank test, p = 0.87). In a Cox regression model, controlling for maternal and gestational age, no significant differences in childhood malignancies were noted between the groups (adjusted HR = 0.82, 95% CI 0.49–1.39, p = 0.47). Conclusions: In our population, twins conceived following infertility treatments are not at an increased risk for childhood malignancies. Full article

Background: Uterine blood flow determines endometrial thickness. This study examined how vaginal sildenafil citrate and estradiol valerate altered endometrial thickness, blood flow, and fertility in infertile women. Methods: This study observed 148 infertile women whose infertility was unexplained. Group 1 comprised 48 patients who received oral estradiol valerate (Cyclo-Progynova 2 mg/12 h white tablets) from day 6 till ovulation was initiated with clomiphene citrate. A number of 50 participants in group 2 received oral sildenafil (Respatio 20 mg/12 h film-coated tablets) for 5 days starting the day after their previous menstrual period and finishing on the day they ovulated with clomiphene citrate. Group 3 was the control group, with 50 patients receiving clomiphene citrate (Technovula 50 mg/12 h tablets) ovulation induction from the 2nd to 7th day of cycle. All patients had transvaginal ultrasounds to determine ovulation, follicle count, and fertility. Miscarriage, ectopic pregnancy, and multiple pregnancies were monitored for three months. Results: The three groups’ mean ETs differed statistically at p = 0.0004. A statistically significant difference was found between the three groups in terms of the number of follicles, with 69% of patients in group 1 having one and 31% having two or more, 76% of patients in group 2 having one and 24% having two or more, and 90% of patients in the control group having one and 10% having two or more (p = 0.038). The clinical pregnancy rates of the three groups were 58%, 46%, and 27%, respectively (p = 0.005). The distribution of all side effects was not statistically different between the three groups. Conclusion: It is possible to claim that adding oral estrogen to clomiphene citrate therapy as an adjuvant therapy can improve endometrial thickness and, as a result, increase the pregnancy rates in unexplained infertility compared to sildenafil, especially in cases where the infertility has lasted less than two years. Most people who take sildenafil end up with a mild headache. Full article

The circulation of progesterone (P4) concentrations of recipients has positive correlations with embryo survival and pregnancy success of embryo transfer (ET) in dairy cows. One strategy to improve P4 concentration is the administration of gonadotropin-releasing hormone (GnRH) or human chorionic gonadotropin (hCG), thereby inducing the formation of accessory corpus luteum (CL). This study aimed at determining the efficacy of GnRH or hCG treatment regarding embryo transfer (ET) and providing a better clinical veterinary practice guidance. A meta-analysis was conducted on the data from 2048 treated recipient cows and 1546 untreated cows. By inducing the formation of accessory CL with GnRH (100 µg), GnRH analogue Buserelin (8–10 µg), or hCG (≥1500 IU) 5–11 days after synchronized ovulation, hCG alone achieved an improvement (RR = 1.39, p < 0.05), while GnRH and GnRH analogue did not result in significant changes (RR = 1.04, p = 0.26). Treatment with GnRH or hCG 5–7 days after synchronized ovulation was associated with increased chances of pregnancy compared with later treatment (11–14 days). Owing to the treatment, the pregnancy rate of cows with very poor fertility (<40%) was improved, while that of cows with good fertility (≥40%) was not affected. Treatment with GnRH or hCG greatly improved pregnancy rates of parous lactating cows (RR = 1.32, p < 0.05) compared with heifers (RR = 1.02, p > 0.05). Additionally, as indicated by pregnancy loss analysis, the treatment had no benefit on late embryo/early fetus survival at days 28–81. In conclusion, the induction of accessory CL with GnRH or hCG may benefit fertility and have important implications for the management of reproductive performance in the dairy industry. Full article

Background: In recent times, different novel GnRH-antagonist protocols with various combinations of gonadotropins and other molecules (e.g., aromatase inhibitors, selective estrogen receptor modulators) have been proposed for expected normal ovarian responders undergoing assisted reproductive treatments. The purpose of this study was to evaluate the effectiveness of a novel ovarian stimulation protocol based on the combination of corifollitropin-alfa plus five days of letrozole in E-NOR women undergoing IVF as compared with a daily recombinant-FSH regimen. Methods: We conducted a retrospective-controlled study on 182 couples undergoing their first IVF attempt. In Group A (experimental), letrozole (2.5 mg daily) was administered from day 2 (up to day 6 of the cycle), followed by corifollitropin-alfa on day 3 and daily recombinant FSH from day 10. In Group B, recombinant FSH from day 2 were administered (150 IU-225 IU daily). Statistical analysis was completed using SPSS Statistics. The primary outcome was the total number of MII oocytes retrieved. Results: Group A showed similar results compared to Group B in terms of MII oocytes, live birth, implantation, and clinical pregnancy rates (p = ns). Nevertheless, the experimental group was associated with a trend towards a higher number of developing follicles, total oocytes, and embryos (p < 0.05) with lower estradiol and progesterone values at ovulation induction compared to Group B, resulting in an increased chance of performing a fresh embryo transfer (p < 0.05). Conclusions: The combination of CFα plus five days of letrozole was associated with a trend towards a higher number of developing follicles, total oocytes, and obtained embryos. Moreover, the experimental protocol resulted in lower estradiol and progesterone values at ovulation induction compared to daily rFSH, with an increased chance of performing a fresh embryo transfer (with no OHSS occurrence). Given the observational design of our study, further well-conducted RCTs are needed. Full article

(1) Background: Intrauterine insemination (IUI) is considered a first-line procedure for infertile or hypo-fertile couples among assisted reproductive techniques. In our retrospective study, we identified variables associated with a successful IUI and the probability of obtaining a pregnancy. This is useful to identify couples with a good chance of obtaining a pregnancy through an IUI procedure (2) Methods: The study was conducted at a university-level fertility clinic in Oradea, Romania. Patients eligible to participate in the study were infertile couples who underwent IUI treatment in the interval between January 2015 and October 2020. (3) Results: In our study, we found that duration of infertility, couple age, endometrium thickness, sperm concentration, and motility are important factors in determining the outcome of IUI. Several demographics were measured for each couple including maternal and paternal age, the type and duration of infertility, the number of procedures, the type of ovarian stimulation, number of follicles, endometrial thickness, the type and day of ovulation induction, associated pathology, tubal patency, and pre/post washes sperm count and progressive sperm motility. (4) Conclusions: Fertility prediction studies are necessary, and an individualized prognostic score should be applied for each couple for tailoring their expectations and better counseling. Full article

Purpose: To evaluate the clinical utility of serum luteinizing hormone (LH) level in predicting frozen embryo transfer (FET) outcomes among the patients with an ovulation induction (OI) cycle. Methods: A total of 250 patients who underwent OI cycle frozen–thawed embryo transfer from January 2018 to June 2020 in Drum Tower Hospital affiliated with Nanjing University Medical School were retrospectively analyzed. The primary outcomes were clinical pregnancy rate and the live birth rate. Results: The results showed that a significant difference in Serum LH level on the day of human chorionic gonadotropin (hCG) administration was observed between the clinical pregnancy group and no clinical pregnancy group (p = 0.002), while there was no significant difference between the live birth group and no live birth group (p = 0.06). Multiple logistic regression analysis of factors related to clinical pregnancy showed serum LH level on the day of hCG administration was related to improved clinical pregnancy rate (OR was 1.02, 95% CI: 1.0–1.03, p = 0.02), while serum LH level had no significant effect on live birth rate. The ROC curves revealed the serum LH level was significantly correlated with clinical pregnancy rate and live birth rate; the cut-off point of serum LH level on the day of hCG administration was 8.46 miu/mL for clinical pregnancy rate (AUC 0.609, p = 0.003). Conclusion: In patients with OI FET, serum LH level on the day of hCG administration might be a biomarker for the prediction of clinical pregnancy. The prediction that patients who underwent OI cycle frozen–thawed embryo transfer with serum LH levels below 8.46 mIU /mL might be pregnant appeared to be meaningful. Full article