Therapeutic potential of endometrial stem cells encapsulated in alginate/gelatin hydrogel to treat of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, often leading to infertility due to anovulation. Recent advances suggest that endometrial stem cells (EnSCs) hold considerable promise for tissue regeneration, which could be pivotal in treating PCOS. To enhance the survival and stabilization of EnSCs within the ovary, the EnSCs were encapsulated in an injectable alginate/gelatin hydrogel (SC-H), which has excellent biocompatibility to support the survival of EnSCs. Polycystic ovary syndrome was induced in female Wistar rats using intraperitoneal injection of letrozole over 21 days. Then the rats were treated with SC, SC-H and clomiphene citrate for one-month post-PCOS induction. The effects of these treatments were evaluated based on changes in body and ovarian weights, inflammatory markers, endocrine profiles, and ovarian histology. The Induction of PCOS led to a significant increase in body and ovarian cyst weight, elevated serum levels of testosterone, luteinizing hormone (LH), and anti-Müllerian hormone (AMH), alongside reduced follicle-stimulating hormone (FSH) and progesterone levels. Histologically, there was a decrease in granulosa cells, immature follicles, and corpus luteum numbers. Treatment with SC and SC-H significantly mitigated these alterations, indicating improved PCOS conditions. Our findings demonstrate that SC and SC-H treatments can effectively ameliorate the symptoms of letrozole-induced PCOS in rats, primarily through their anti-inflammatory effects. This study lays the groundwork for potential clinical applications of EnSCs encapsulated in alginate/gelatin hydrogel as a novel therapeutic strategy for PCOS, highlighting the importance of biomaterials in stem cell-based therapies.

Effectiveness of Acupuncture for Infertility in Patients with Polycystic Ovary Syndrome: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: This study employs a network meta-analysis method to investigate the clinical effectiveness of acupuncture in patients with polycystic ovary syndrome (PCOS) experiencing infertility. METHODS: Prospective randomized controlled trials (RCTs) of clomiphene citrate (CC) and letrozole (LE) combined with acupuncture in PCOS infertility patients were identified through computerized searches in databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chongqing VIP Database. The search period was set from inception until August 1, 2023, with no language restrictions. Two researchers screened articles, extracted data, and independently assessed the risk of bias in eligible trials. Data were analyzed and visualized using the R software gemtc package. With patients with medication treatment only set as controls, a meta-analysis was performed to investigate the difference in the pregnancy outcomes of the PCOS patients following medication amalgamated with different acupuncture treatments, namely, manual acupuncture (MA), electroacupuncture (EA), and warm acupuncture (WA). RESULTS: The serum concentrations of follicle-stimulating hormone (FSH) did not exhibit significant changes following acupuncture treatments. Notably, acupuncture-based medication treatment significantly reduced serum levels of luteinizing hormone (LH) and elevated the testosterone (T) concentrations of patients when compared to medication treatment alone. Patients also showed significantly escalated serum estradiol (E2) levels after receiving CC integrated with acupuncture than those given monotherapy of CC. The combined regimen of medication and acupuncture appeared to improve the pregnancy outcomes compared to the monotherapy of medication, as evidenced by the significantly increased success rate of pregnancy. Furthermore, the treatment combination of CC plus WA and LE plus MA yielded the highest probability of achieving the best pregnancy outcomes. CONCLUSION: For PCOS infertility patients, acupuncture, as a complementary treatment to CC and LE, holds advantages in improving reproductive hormone levels and enhancing pregnancy success rates. The highest probability of achieving the best pregnancy outcomes is associated with the treatment combination of CC with WA and LE with MA.

Competence of Combined Low Dose of Human Chorionic Gonadotropin (HCG) and Clomiphene Citrate (CC) Versus Continued CC during Ovulation Induction in Women with CC-Resistant Polycystic Ovarian Syndrome: A Randomized Controlled Trial.

Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5-18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226.

Off-label use of clomiphene citrate to treat anabolic androgenic steroid induced hypogonadism upon cessation among men (CloTASH) - A pilot study protocol.

Background: Non-prescribed anabolic androgenic steroid (AAS) use is associated with AAS-induced hypogonadism (ASIH), and metabolic, cardiovascular, and mental health risks. Symptoms of ASIH (fatigue, depression, anxiety, sexual dysfunction) are hard to endure following cessation, but there is no consensus on whether endocrine treatment should be used to treat ASIH. This proof-of-concept study aims to explore safety of off-label clomiphene citrate therapy, whether the treatment will reduce the symptoms of androgen deficiency, and to study changes in health risks after cessation. Methods: In this open-labeled non-randomized off-label hormone intervention pilot study, we shall include males with AAS dependence intending to cease use. The 16-week intervention included clomiphene citrate, transdermal testosterone gel for the first four weeks and optional human chorionic gonadotropin (hCG) from week 4 if low treatment response. Measures of physical and mental health will be examined from ongoing AAS use, during the intervention, and at 6- and 12 months post cessation. Change in self-reported symptoms of hypogonadism and other withdrawal symptoms will be compared with data from a group of men who ended AAS use temporarily without the medical intervention. The study may provide valuable clinical insights and may be used to inform the design of future intervention studies.

Strong Early Impact of Letrozole on Ovulation Induction Outperforms Clomiphene Citrate in Polycystic Ovary Syndrome.

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.

Drainage by Ovarian Incision for the Treatment of Massive Ovarian Edema Torsion During Pregnancy.

Massive ovarian edema (MOE) is a rare benign condition presenting as unilateral ovarian enlargement with stromal edema, and only a limited number of MOE cases during pregnancy have been reported. MOE is often complicated by ovarian torsion, which requires detorsion. Although the diagnosis of MOE can be made using ultrasound and magnetic resonance imaging, its rarity makes diagnosis difficult, usually leading to overtreatment. Preserving the ovary in the treatment of MOE torsion is essential, and consideration of oophoropexy after detorsion is often reported. However, fixing an enlarged ovary to the pelvic wall in the limited space of the pelvis is challenging. Herein, we present a case of MOE of the right ovary diagnosed at the fifth week of gestation after ovulation induced by clomiphene citrate. Torsion of the ovary occurred in the seventh week. We achieved preservation of the ovary through laparoscopic surgery with detorsion and drainage by making a small incision to the enlarged ovary, resulting in an immediate size reduction. There was no recurrence of torsion or MOE throughout the pregnancy, and the patient gave birth in the 39th week of gestation. This is the third reported case of MOE after ovulation using clomiphene citrate, and it highlights the effectiveness of treatment with detorsion and a small incision of the ovary via laparoscopic surgery in patients with MOE torsion during pregnancy.

Infertility Challenge in a Cryptozoospermic Patient With Y Chromosome Microdeletion.

A couple is usually diagnosed with infertility if they have regular, unprotected sexual activity for a year or longer and are unable to conceive. Male infertility can be categorised into three types: obstructive infertility, non-obstructive infertility, and coital infertility. A major contributing factor for infertility in men is Y chromosome microdeletion, which is a non-obstructive infertility that involves problems related to sperm production. Deletions in the azoospermia factor region known as azoospermia factor a (AZFa), azoospermia factor b (AZFb), and azoospermia factor c (AZFc) loci independently or together which are situated on the Y chromosome cause a disturbance and alteration that are linked to either a reduction in sperm count, known as oligozoospermia, or the absence of sperm cells in the semen sample, referred to as azoospermia. Observations indicate that individuals with AZFc microdeletion may display irregularities in endocrine hormones. Men experiencing hormonal abnormalities affecting sperm production may receive treatment with clomiphene citrate. In cases of azoospermia and numerous cryptozoospermic patients, intracytoplasmic sperm injection is frequently considered the primary therapeutic approach.

Clomiphene citrate as a new modality in management of vaginal bleeding with depomedroxyprogesterone acetate (DMPA): A randomized controlled trial.

BACKGROUND: Depo-medroxyprogesterone acetate (DMPA) functions as a contraceptive method by inhibiting the secretion of gonadotropins, which prevents follicular maturation and ovulation, as well as thinning of the endometrium leading to unscheduled vaginal bleeding and subsequent discontinuation of DMPA. Our study aimed to evaluate the efficacy and safety of clomiphene citrate (CC) in stopping bleeding among DMPA users. MATERIALS AND METHODS: We randomly assigned 200 DMPA users using a computer-generated random numbers table in a 1:1 ratio to one of two groups; the study group, which received CC at a dose of 50 mg twice daily for five days (n = 100), and the control group, which received a placebo for five days (n = 100). Our primary outcome measure was the onset and duration of bleeding cessation. Secondary outcomes included endometrial thickness, recurrence of vaginal bleeding, and any reported side effects associated with CC use. RESULTS: Clomiphene citrate significantly resulted in early cessation of vaginal bleeding in 83 % of the patients, which continued for three months of follow-up. In addition, the recurrence of vaginal bleeding was significantly reduced in the CC group compared to the control group (11 % vs. 67 %; p < 0.001). Endometrial thickness was significantly greater in the CC group than in the control group (p < 0.001). Breast tenderness was more frequently reported in the study group, with no difference in dyspareunia between the two groups. CONCLUSIONS: Clomiphene citrate is effective in controlling bleeding among DMPA users. Further studies are encouraged to confirm our findings.

Long-term use of clomiphene in male macroprolactinomas with persistent hypogonadism.

BACKGROUND: Men with macroprolactinoma can present persistent hypogonadism despite normoprolactinemia achieved with clinical and/or neurosurgical treatment. Usually, testosterone replacement therapy is indicated. Nevertheless, although off-label, clomiphene citrate (CC), a selective estrogen receptor modulator, has also been used, mainly when fertility is an issue. The aim of this study is to evaluate the effectiveness of CC in recovering the gonadal axis in men with macroprolactinoma, with or without hyperprolactinemia, and evaluate its safety as a long-term therapy. METHODS: This is a retrospective study including 10 men with macroprolactinoma on cabergoline treatment and persistent hypogonadism. All patients received initially 50 mg/d of CC. RESULTS: The median age at diagnosis of prolactinomas was 34 (range, 26-60) years old. All patients were treated with cabergoline at a median maximum dose of 2 (1-7) mg/week, with a median time of treatment of 8.5 (2-15) years. Prolactin was still above the normal range when CC was introduced only in two patients. The mean duration of CC therapy was 3.2 (±2.8) years. Prolactin levels maintained stable (p = 0.252) and testosterone increased (p = 0.027) significantly on CC therapy. Tumor size remained stable. Eight patients (80%) maintained testosterone above 300 ng/dL and were classified as responders. Three responders succeeded in using a lower dose of CC and one of them completed withdrawal CC and maintained eugonadism. There were no side effects or safety concerns reported. CONCLUSION: CC should be seen as a safe treatment option for men with macroprolactinoma and persistent hypogonadism.

Clomiphene Citrate Administered in Periconception Phase Causes Fetal Loss and Developmental Impairment in Mice.

Clomiphene citrate is a common treatment for ovulation induction in subfertile women, but its use is associated with elevated risk of adverse perinatal outcomes and birth defects. To investigate the biological plausibility of a causal relationship, this study investigated the consequences in mice for fetal development and pregnancy outcome of periconception clomiphene citrate administration at doses approximating human exposures. A dose-dependent adverse effect of clomiphene citrate given twice in the 36 hours after mating was seen, with a moderate dose of 0.75 mg/kg sufficient to cause altered reproductive outcomes in 3 independent cohorts. Viable pregnancy was reduced by 30%, late gestation fetal weight was reduced by 16%, and ∼30% of fetuses exhibited delayed development and/or congenital abnormalities not seen in control dams, including defects of the lung, kidney, liver, eye, skin, limbs, and umbilicus. Clomiphene citrate also caused a 30-hour average delay in time of birth, and elevated rate of pup death in the early postnatal phase. In surviving offspring, growth trajectory tracking and body morphometry analysis at 20 weeks of age showed postweaning growth and development similar to controls. A dysregulated inflammatory response in the endometrium was observed and may contribute to the underlying pathophysiological mechanism. These results demonstrate that in utero exposure to clomiphene citrate during early pregnancy can compromise implantation and impact fetal growth and development, causing adverse perinatal outcomes. The findings raise the prospect of similar iatrogenic effects in women where clomiphene citrate may be present in the periconception phase unless its use is well-supervised.

Recuperación de la espermatogénesis tras el abuso de esteroides anabólicos androgénicos en varones. Revisión sistemática de la literatura / Recovery of spermatogenesis after androgenic anabolic steroids abuse in men. A systematic review of the literature

Objetivo El objetivo de esta revisión sistemática es identificar el tratamiento óptimo para la infertilidad masculina derivada del abuso de esteroides anabólicos androgénicos (EAA). Métodos Se llevó a cabo una revisión sistemática según la declaración Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Se incluyeron estudios que comparaban distintos protocolos para la recuperación de la espermatogénesis tras el uso de EAA. Resultados Un total de 13 estudios que investigaban diferentes protocolos para recuperar la espermatogénesis en pacientes con abuso de EAA cumplieron los criterios de inclusión. Entre los agentes disponibles que demostraron eficacia en el reestablecimiento de la espermatogénesis se encuentran las gonadotropinas inyectables, los moduladores selectivos de los receptores de estrógenos (SERM) y los inhibidores de la aromatasa (AI), pero su uso apenas ha sido descrito en la literatura. Conclusiones Los médicos deben conocer los efectos adversos que los EAA pueden tener sobre la espermatogénesis. La infertilidad asociada a estos agentes puede ser de carácter reversible, pero la producción de espermatozoides puede tardar más de un año en normalizarse. Tanto el tratamiento conservador como el agresivo pueden estimular la espermatogénesis con resultados satisfactorios. Se requiere una mayor comprensión de la endocrinología reproductiva masculina y datos de alta calidad sobre la recuperación de la espermatogénesis tras el abuso de EAA. (AU)

Objective This systematic review aims to evaluate the optimal treatment for male infertility resulting from Anabolic Androgenic Steroids (AAS) abuse. Methods A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies that compared different protocols for the recovery of spermatogenesis in patients after AAS use were included. Results 13 studies investigating different protocols to restore spermatogenesis in patients with AAS abuse met the inclusion criteria. The available agents that showed restoration of spermatogenesis include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their use is still poorly described in the literature. Conclusions Clinicians need to be aware of the detrimental effects of AAS on spermatogenesis. AAS-associated infertility may be reversible, but sperm production may take over a year to normalize. Both conservative and aggressive treatment can boost spermatogenesis with positive results. Further understanding of male reproductive endocrinology and high-quality data on the field of restoration of spermatogenesis after AAS abuse are warranted. (AU)

Efficacy of Letrozole vs Clomiphene Citrate for induction of ovulation in women with polycystic ovarian syndrome.

Objective: To compare the efficacy of letrozole vs Clomiphene citrate for ovulation induction in PCOS women. Methods: This double blind randomized controlled trial was conducted at Services Hospital, Lahore, from January 2016 to December 2020. Total 220 patients, diagnosed with PCOS according to Rotterdam criteria were randomly assigned into two groups after taking informed consent. The women were followed for ovulation, pregnancy and live birth rates in the next five consecutive menstrual cycles with either clomiphene citrate or letrozole. Results: Letrozole had significantly better pregnancy rate (29.0% vs 15.4% p-value 0.015), monofollicular development (77.2% vs 52.7% p-value 0.000) and live birth rate (25.4% vs 10.9% p-value 0.005) as compared to clomiphene citrate. There was no difference between the two groups in ovulation rate (68.1% vs 63.6%, p-value 0.477), early pregnancy loss (3.6% vs 4.5% p-value 0.734), and twin pregnancy (0.0% vs 1.81% p-value 0.155). There was no ectopic pregnancy and no congenital anomalies in both groups. Hot flushes were higher in clomiphene group (31.8% vs 12.7% p-value 0.001) while fatigue (30.9% vs 8.1% p-value 0.000) and dizziness (21.8% vs 10.0% p-value 0.029) was higher with letrozole but these were well tolerated. Conclusion: Letrozole is better treatment choice than clomiphene citrate in PCOS women with infertility in terms of pregnancy and live birth rate.ClinicalTrials.gov Identifier: NCT05702957.

Clinical and neonatal outcomes of complete zona pellucida removal by laser-assisted hatching after single vitrified-warmed blastocyst transfer.

Laser-assisted hatching (LAH) is a widely used and unavoidable technique in assisted reproductive technology after frozen embryo transfer (FET). We aimed to investigate the safety and efficacy of completely ZP (zona pellucida) removed by an assisted laser group compared to an intact group after FET. This retrospective study involved 320 SVBT  single vitrified-warmed blastocyst transfers of 213 patients who underwent clomiphene citrate (CC) based minimal stimulation protocol. This study compared 160 SVBT with ZP that were completely removed using laser-assisted (laser beams of 10-15, a wavelength of 1.48 µm, and duration of 1.8-2.2 ms) to 160 cases of intact SVBT. Fisher's exact test, chi-squared test, and logistic regression are used for statistical analysis. The women's age, cause of infertility, BMI, transferred embryo day, insemination methods, and blastocyst grade were not significantly different between two groups. The implantation rate (66.2% vs. 51.2%, P < 0.01), the clinical pregnancy rate (CPR, 52.5% vs. 39.3%, P = 0.01), and the live birth rate (LBR, 43.7% vs. 29.3%, P < 0.01) were significantly higher in the completely ZP removed than the intact group. In logistic regression analysis, the laser-assisted hatching group showed about 2 times higher implantation rate and CPR and LBR than the control group. But miscarriage, gestational weeks, gender, birth weight, and twin births were insignificant between two groups. Our study suggests ZP free embryo transfer by assisted laser is more effective and safer than intact embryo transfer.

Recovery of spermatogenesis after androgenic anabolic steroids abuse in men. A systematic review of the literature.

OBJECTIVE: This systematic review aims to evaluate the optimal treatment for male infertility resulting from Anabolic Androgenic Steroids (AAS) abuse. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies that compared different protocols for the recovery of spermatogenesis in patients after AAS use were included. RESULTS: 13 studies investigating different protocols to restore spermatogenesis in patients with AAS abuse met the inclusion criteria. The available agents that showed restoration of spermatogenesis include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their use is still poorly described in the literature. CONCLUSIONS: Clinicians need to be aware of the detrimental effects of AAS on spermatogenesis. AAS-associated infertility may be reversible, but sperm production may take over a year to normalize. Both conservative and aggressive treatment can boost spermatogenesis with positive results. Further understanding of male reproductive endocrinology and high-quality data on the field of restoration of spermatogenesis after AAS abuse are warranted.

Comparison of Letrozole and Clomiphene Citrate in Pregnancy Outcomes in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

Clomiphene citrate (CC) and letrozole are the predominant medical interventions for the management of infertility in patients with polycystic ovary syndrome (PCOS). To comprehensively summarize the evidence, a systematic review and meta-analysis of randomized clinical trials (RCTs) was carried out to assess the effect of letrozole and CC on pregnancy outcomes in PCOS patients. We searched PubMed/MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials from inception to January 2023. We included RCTs conducted on PCOS women comparing letrozole to CC and assessing endometrial thickness, the number and size of follicles, and ovulation and pregnancy rates. The endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) using the random-effects model. Heterogeneity was examined using the I2 statistic. Fifty trials met our inclusion criteria. The mean endometrial thickness was significantly higher in the letrozole group compared to CC group (SMD: 0.89; 95% CI: 0.49, 1.28; I2=97.72%); however, the number of follicles was higher in the CC group (SMD: -0.56; 95% CI: -0.96, -0.17; I2=96.34%). Furthermore, letrozole intake induced higher ovulation rate (RR: 1.20; 95% CI: 1.13, 1.26; I2=54.49%) and pregnancy rate (RR: 1.44; 95% CI: 1.28, 1.62; I2=65.58%) compared to CC. Compared to CC, letrozole has a positive effect on endometrial thickness, monofollicular development, and ovulation and pregnancy rates suggesting that letrozole may be a strong alternative to CC as a first-line medical intervention for chronic anovulation in PCOS women. Larger studies are warranted to further clarify these findings.

Prevention of moderate and severe ovarian hyperstimulation syndrome: a guideline.

Ovarian hyperstimulation syndrome is a serious complication associated with assisted reproductive technology. This systematic review aims to identify who is at high risk for developing ovarian hyperstimulation syndrome, along with evidence-based strategies to prevent it and replaces the document of the same name last published in 2016.

Clomiphene citrate plus letrozole versus clomiphene citrate alone for ovulation induction in infertile women with ovulatory dysfunction: a randomized controlled trial.

BACKGROUND: The aim of this study was to compare the efficacy of the combination of clomiphene citrate (CC) and letrozole to that of CC alone in inducing ovulation in infertile women with ovulatory dysfunction. METHODS: A randomized controlled trial was conducted at a single academic medical center between November 2020 and December 2021. Anovulatory infertility females, aged 18 to 40, were evenly distributed by a computer-generated block of four into two treatment groups. A "combination group" received a daily dose of CC (50 mg) and letrozole (2.5 mg), while a "CC-alone group" received a daily dose of CC alone (50 mg). The study medications were administered on days 3 through 7 of menstrual cycle. The primary outcome was the ovulation rate, defined by serum progesterone levels exceeding 3 ng/mL at the mid-luteal phase. The secondary outcomes were ovulation induction cycle characteristics, endometrial thickness, conception rate, and adverse events. RESULTS: One hundred women (50 per group) were enrolled in the study. The mean age was not significantly different in both groups: 31.8 years in the combination group and 32.4 years in the CC-alone groups (P = 0.54). The prevalence of polycystic ovary syndrome in the combination and CC-alone groups was 48% and 44%, respectively (P = 0.841). According to intention-to-treat analysis, the ovulation rates were 78% and 70% in the combination and CC-alone groups, respectively (P > 0.05). There was no significant difference in the mean endometrial thickness or the number of dominant follicles of the groups. No serious adverse events were observed in either group. CONCLUSIONS: Our study found no significant difference between the combination of CC and letrozole and CC alone in inducing ovulation in infertile women with ovulatory dysfunction in one cycle. The small number of live births precluded any meaningful statistical analysis. Further studies are needed to validate and extend our findings beyond the scope of the current study. TRIAL REGISTRATION: The study was registered at https://www.thaiclinicaltrials.org with the following number: TCTR20201108004 and was approved on 08/11/2020.

Strong social disparities in access to IVF/ICSI despite free cost of treatment: a French population-based nationwide cohort study.

BACKGROUND: Access to IVF/ICSI is facilitated when the financial barrier is removed. In a national context where in vitro fertilisation (IVF)/intracytoplasmic sperm Injection (ICSI) treatment is cost-free, how many women do not access IVF/ICSI and what are the factors associated with non-access? METHODS: Using French national health insurance databases, the cohort included 20,240 women aged 18-43 years living in France who underwent unsuccessful treatment (no pregnancy) with clomiphene citrate (CC) and/or gonadotropins with treatment started between January and August 2016. The outcome measure was non-access to IVF/ICSI during the 24-month following start of infertility care. Factors associated with non-access to IVF/ICSI were explored using mixed effects logistic regression. RESULTS: In the cohort, 65.4% of women did not access IVF/ICSI. In multivariable analysis, non-access to IVF/ICSI was higher in younger women (18-25 years: (OR 2.17, 95% CI: 1.85-2.54) and in older women (40-43 years: (OR=3.60, 95% CI: 3.25-3.98)). Non-access was higher among women below the poverty line (OR=3.76, 95% CI: 3.34-4.23) and showed a significant upward trend with increasing deprivation of place of residence. Distance to the nearest fertility centre was not significantly associated with non-access to IVF/ICSI. CONCLUSIONS: In a national context of cost-free ART treatment, a large proportion of women did not access treatment, with a strong social gradient that raises important issues. We need to understand the underlying social mechanisms to develop an efficient and equitable health policy regarding infertility care.

Clomiphene Citrate in the Management of Infertility in Oligospermic Obese Men with Hypogonadism: Retrospective Pilot Study.

Background and Objectives: Obesity is a significant risk factor for hypogonadism and infertility that is further associated with reduced semen quality. The aim of this study is to evaluate the effect of clomiphene citrate (CC), prescribed for treating infertility, on serum testosterone and semen parameters, particularly in oligospermic obese hypogonadal men. Materials and Methods: A retrospective analysis of data related to men (n = 53) who underwent CC treatment for infertility and hypogonadism (testosterone < 300 ng/dL) was performed. Patients with obesity (BMI ≥ 30 kg/m2) and sperm concentration ≤ 15 × 106/mL were included for analysis. Results: The overall results showed that, in oligospermic obese men (n = 31), treatment with CC significantly improved baseline sperm concentration (4.5 ± 6.8 × 106/mL vs. 11.4 ± 15.5 × 106/mL, p < 0.05) and motility (31.5% ± 21.5% vs. 42.6% ± 14.7%, p < 0.05). Furthermore, subsequent examination of oligospermic hypogonadal obese men treated with CC (n = 13) revealed substantial improvements in baseline serum testosterone levels (193.8 ± 59.3 ng/dL vs. 332.7 ± 114.8 ng/dL, p < 0.05) along with an increase in sperm concentration, total motility, and normal morphology. Conclusions: The results of this retrospective study suggest that CC treatment not only improves chances of fertility outcomes by substantially improving semen parameters but also increases total serum testosterone levels in oligospermic obese men without any supplemental and expensive testosterone replacement therapy.

[Medical treatments for male infertility]. / Traitements médicaux de l'homme infertile.

BACKGROUND: Treatments to stimulate spermatogenesis and antioxidant food supplements are often offered to infertile patients either before sperm extraction surgery to improve results, or as part of medically assisted reproduction or spontaneous fertility to increase the likelihood of a live birth. METHODS: A bibliographic search limited to English-language literature on men published before 5/2023 was carried out, including clinical trials, literature reviews and meta-analyses on spermatogenesis-stimulating molecules and antioxidant treatments. RESULTS: Several medical treatments seem capable of improving male fertility: they act mainly by stimulating spermatogenesis through hormones, or by reducing the effects of oxidative stress. With regard to oligoasthenozoospermia, the literature shows that certain hormonal treatments stimulating spermatogenesis are useful. In the case of non-obstructive azoospermia, the value of treatment depends on the patient's FSH and testosterone levels. AOX supplementation appears to improve certain spermogram parameters and have an impact on pregnancy and live birth rates. CONCLUSION: This review should help urologists gain a better understanding of the various medical treatments and enable them to define an appropriate therapeutic strategy, tailored to the patient and the couple, in order to obtain the best results.