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OBJECTIVE: To compare letrozole in combination with gonadotropins versus letrozole monotherapy in ovulation induction and clinical pregnancy among infertile women with polycystic ovarian syndrome (PCOS).
METHODS: Several databases were searched for available clinical trials from inception until March 2023. We selected randomized controlled trials (RCTs) that compared sequential letrozole/gonadotropin versus letrozole alone among infertile women who met the Rotterdam criteria for PCOS. RevMan software was used to perform our meta-analysis. Our primary outcomes were ovulation and clinical pregnancy rates. Our secondary outcomes were endometrial thickness, number of mature follicles (diameter ≥ 18 mm), and incidence of miscarriage and ovarian hyperstimulation syndrome (OHSS).
RESULTS: Six RCTs were retrieved with a total number of 723 patients. The ovulation and clinical pregnancy rates were significantly higher among the letrozole/gonadotropin group versus the letrozole monotherapy group (p < 0.001). In addition, there were significant improvements in endometrial thickness and number of mature follicles in the letrozole/gonadotropin group. There were no significant differences between the two groups regarding incidence of miscarriage and ovarian hyperstimulation syndrome.
CONCLUSIONS: Letrozole in combination with gonadotropin is superior to letrozole alone in improving ovulation induction and clinical pregnancy among PCOS patients. More trials are required to confirm our findings.

OBJECTIVE: Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical treatment with testosterone promotes virilization but not testicular growth or spermatogenesis. To quantify treatment practices and efficacy, we systematically reviewed all studies investigating gonadotropins for the achievement of pubertal outcomes in males with hypogonadotropic hypogonadism.
METHODS: Systematic review and meta-analysis.
METHODS: A systematic review of Medline, Embase, Global Health, and PsycINFO databases in December 2022. Risk of Bias 2.0/Risk Of Bias In Non-randomized Studies of Interventions/National Heart, Lung, and Blood Institute tools for quality appraisal. Protocol registered on PROSPERO (CRD42022381713).
RESULTS: After screening 3925 abstracts, 103 studies were identified including 5328 patients from 21 countries. The average age of participants was <25 years in 45.6% (n = 47) of studies. Studies utilized human chorionic gonadotropin (hCG) (n = 93, 90.3% of studies), human menopausal gonadotropin (n = 42, 40.8%), follicle-stimulating hormone (FSH) (n = 37, 35.9%), and gonadotropin-releasing hormone (28.2% n = 29). The median reported duration of treatment/follow-up was 18 months (interquartile range 10.5-24 months). Gonadotropins induced significant increases in testicular volume, penile size, and testosterone in over 98% of analyses. Spermatogenesis rates were higher with hCG + FSH (86%, 95% confidence interval [CI] 82%-91%) as compared with hCG alone (40%, 95% CI 25%-56%). However, study heterogeneity and treatment variability were high.
CONCLUSIONS: This systematic review provides convincing evidence of the efficacy of gonadotropins for pubertal induction. However, there remains substantial heterogeneity in treatment choice, dose, duration, and outcomes assessed. Formal guidelines and randomized studies are needed.

Controlled ovarian hyperstimulation (COH) is an essential for in vitro fertilization-embryo transfer (IVF-ET) and an important aspect of assisted reproductive technology (ART). Individual starting doses of gonadotropin (Gn) is a critical decision in the process of COH. It has a crucial impact on the number of retrieved oocytes, the cancelling rate of ART cycles, and complications such as ovarian hyperstimulation syndrome (OHSS), as well as pregnancy outcomes. How to make clinical team more standardized and accurate in determining the starting dose of Gn is an important issue in reproductive medicine. In the past 20 years, research teams worldwide have explored prediction models for Gn starting doses. With the integration of artificial intelligence (AI) and deep learning, it is hoped that there will be more suitable predictive model for Gn starting dose in the future.

UNASSIGNED: To appraise the current randomized clinical trials (RCTs) for evidence of the association of growth hormone (GH) with improved outcomes in infertile women with diminished ovarian reserve (DOR) undergoing in vitro fertilization (IVF).
UNASSIGNED: Relevant RCTs published in Chinese or English were identified through a comprehensive search of nine databases from the period of database inception to April 20, 2023. We included trials investigating adjuvant GH during ovarian stimulation and reported the subsequent outcomes. The group with adjuvant GH treatment and the group without adjuvant GH treatment were set up as the trial and control groups, respectively. The quality of RCTs was measured according to the Cochrane Collaboration Handbook.
UNASSIGNED: Of the 579 studies initially identified, 10 RCTs comprising 852 infertile women with DOR were included. The GH dose of individual trials ranged between 3 and 5 IU/day. Overall, we judged the trials to be at high risk of bias in the blinding domain. Pooled results showed that GH was associated with an increased clinical pregnancy rate (RR = 1.63, 95%CI [1.31, 2.03], p < 0.0001) and a greater number of oocytes retrieved (MD = 0.91, 95%CI [0.47, 1.35], p < 0.0001). Favorable associations were also observed when ovarian stimulation was combined with GH therapy for improving the optimal embryos rate (RR = 1.84, 95%CI [1.30, 2.59], p = 0.0005) and the number of optimal embryos (MD = 0.28, 95%CI [0.08, 0.48], p = 0.005) along with reducing the cycle cancellation rate (RR = 0.46, 95%CI [0.24, 0.89], p = 0.02). Moreover, GH resulted in an increase in the fertilization rate (RR = 1.33, 95%CI [1.18, 1.50], p < 0.00001) and the embryo implantation rate (RR = 1.56, 95%CI [1.21, 2.01], p = 0.0006). In addition, there was a significant enhancement in estradiol levels (SMD = 1.18, 95%CI [0.46, 1.91], p = 0.001) and endometrial thickness (MD = 0.75, 95%CI [0.41, 1.09], p < 0.0001) on the day of hCG. With regard to the total number of days and total dose of gonadotrophins used, GH treatment was correlated with shorter days (MD = -0.26, 95%CI [-0.46, -0.06], p = 0.01) and lower dose (MD = -460.97, 95%CI [-617.20, -304.73], p < 0.00001) of gonadotrophins applied during ovarian stimulation. Furthermore, GH in conjunction with the GnRH antagonist protocol was more conducive to improving the number of oocytes retrieved when compared with the GnRH agonist protocol (p < 0.0001). Moreover, a notable association was also seen in IVF combined with GH more than or equal to 4.5 IU/day to increase the number of optimal embryos and estradiol levels on the day of hCG (p < 0.05).
UNASSIGNED: For infertile women with DOR undergoing IVF, adjuvant treatment with GH during ovarian stimulation protocols showed better clinical outcomes, shorter days and lower dosages of gonadotrophin required. Furthermore, well-designed RCTs are needed to verify our results in the future.
UNASSIGNED: https://www.crd.york.ac.uk PROSPERO (CRD42023421739).

Genetic variants are predisposing factors to polycystic ovary syndrome (PCOS), a multifactorial condition that often gets triggered due to various environmental factors. The study investigates the association of the variants of genes that are involved in the steroidogenesis pathway or gonadotropin pathway with the risk of PCOS. Appropriate keywords for predetermined genes were used to search in PubMed, Google Scholar, Science Direct, and Central Cochrane Library up to January 11, 2023. PROSPERO (CRD42022275425). Inclusion criteria: (a) case-control study; (b) genotype or allelic data. Exclusion criteria were: (a) duplicate studies; (b) clinical trials, systematic reviews, meta-analysis or conference abstract, case reports; (c) other than the English language; (d) having insufficient data; e) genetic variants for which meta-analysis has been reported recently and does not have a scope of the update. Various genetic models were applied as per data availability. Overall 12 variants of 7 genes were selected for the analysis. Relevant data were extracted from 47 studies which include 10,584 PCOS subjects and 16,150 healthy controls. Meta-analysis indicates a significant association between TOX3 rs4784165 [ORs = 1.08, 95% CI (1.00-1.16)], HMGA2 rs2272046 [ORs = 2.73, 95% CI (1.97-3.78)], YAP1 rs1894116 [OR = 1.22, 95% CI (1.13-1.33)] and increased risk of PCOS. Whereas FSHR rs2268361 [ORs = 0.84, 95% CI (0.78-0.89)] is associated with decreased PCOS risk. When sensitivity analysis was carried out, the association became significant for CYP19 rs700519 and FSHR rs6165 under an additive model. In addition, C9Orf3 rs3802457 became significantly associated with decreased PCOS risk with the removal of one study. Insignificant association was observed for CYP19A (rs2470152), FSHR (rs2349415, rs6166), C9Orf3 (rs4385527), GnRH1 (rs6185) and risk of PCOS. Our findings suggest association of CYP19A (rs700519), TOX3 (rs4784165), HMGA2 (rs2272046), FSHR (rs6165, rs2268361), C9orf3 (rs3802457), and YAP1 (rs1894116) with risk for PCOS.

The aim of this systematic review and meta-analysis was to quantify the effect of random start ovarian stimulation (RSOS) compared with conventional start ovarian stimulation (CSOS) in cancer patients before gonadotoxic treatment. The final analytical cohort encompassed 688 RSOS and 1076 CSOS cycles of cancer patients before gonadotoxic treatment. Eleven studies were identified by database searches of MEDLINE, Cochrane Library and cited references. The primary outcomes of interest were the number of oocytes and mature oocytes collected, the number of embryos cryopreserved and the metaphase II (MII)-antral follicle count (AFC) ratio. The studies were rated from medium to high quality (from 6 to 9) according to the Newcastle-Ottawa Quality Assessment Scale. The two protocols resulted in similar numbers of oocytes collected, MII oocytes, embryos available for cryopreservation and comparable MII-AFC and fertilization rates. The duration of ovarian stimulation was longer (standardized mean difference [SMD] 0.35, 95% CI 0.09 to 0.61; P = 0.009) and gonadotrophin consumption was higher (SMD 0.23, 95% CI 0.06 to 0.40; P = 0.009) in RSOS compared with CSOS. This systematic review and meta-analysis show that the duration of stimulation is longer, and the total gonadotrophin consumption is higher in cancer patients undergoing RSOS compared with those undergoing CSOS, with no significant effect on mature oocyte yield.

The development of an ovulatory follicle is a fundamental premise for any reproductive management program that aims to optimize fertility in cattle. Controlling follicular development comprises the synchronized emergence of a new follicular wave, selection and growth of the dominant follicle, and synchronized ovulation of a high-quality oocyte. All these follicular events, primarily driven by gonadotropin secretion, occur under a very dynamic hormonal environment. In this sense, controlling follicular development demands essentially a precise manipulation of the hormonal environment to modulate gonadotropin secretion. Furthermore, the effectiveness of hormonal manipulation strategies in the management of follicular development depends on specific particularities of each situation, which can vary widely according to genetic groups (Bos taurus vs Bos indicus), nutritional, metabolic, and reproductive status. In this regard, the constant search for the refined synchrony between the hormonal treatments and reproductive events, considering these distinctions and particularities, have provided valuable information that contributed to the development of efficient reproductive programs. This manuscript discusses the physiological bases behind the development of fine-tuned timed-artificial insemination protocols for beef and dairy cattle that resulted in great improvements in reproductive efficiency of beef and dairy herds.

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.

OBJECTIVE: We aimed to evaluate aspects of pubertal development to identify the most reliable clinical sign of pubertal onset in males.
METHODS: We performed a mini review of the literature.
RESULTS: In 1951 Reynolds and Wines categorised pubic hair growth and genital development in five stages by visual inspection. Today the Tanner scale is used to assess the five stages of pubertal development, The second genital stage, characterised by enlargement of the scrotum defines pubertal onset in males. Testicular volume may be evaluated by using a calliper or by ultrasound scan. The Prader orchidometer, described in 1966, offers a method for evaluating testicular growth by palpation. Pubertal onset is commonly defined as testicular volume >3 or ≥4 mL. The development of sensitive laboratory methods has enabled studies analysing hormonal activity in the hypothalamus-pituitary-gonadal axis. We review the relationships between physical and hormonal signs of puberty. We also discuss the results of studies assessing different aspects of pubertal development with a focus on identifying the most reliable clinical sign of pubertal onset in males.
CONCLUSIONS: A substantial amount of evidence supports testicular volume of 3 mL as the most reliable clinical sign of male pubertal onset.