Establishment and validation of a nomogram model for predicting ovulation in the PCOS women.

BACKGROUND: The mechanisms underlying ovulatory dysfunction in PCOS remain debatable. This study aimed to identify the factors affecting ovulation among PCOS patients based on a large sample-sized randomized control trial. METHODS: Data were obtained from a multi-centered randomized clinical trial, the PCOSAct, which was conducted between 2011 and 2015. Univariate and multivariate analysis using binary logistic regression were used to construct a prediction model and nomogram. The accuracy of the model was assessed using receiver operating characteristic (ROC) curves and calibration curves. RESULTS: The predictive variables included in the training dataset model were luteinizing hormone (LH), free testosterone, body mass index (BMI), period times per year, and clomiphene treatment. The ROC curve for the model in the training dataset was 0.81 (95% CI [0.77, 0.85]), while in the validation dataset, it was 0.7801 (95% CI [0.72, 0.84]). The model showed good discrimination in both the training and validation datasets. Decision curve analysis demonstrated that the nomogram designed for ovulation had clinical utility and superior discriminative ability for predicting ovulation. CONCLUSIONS: The nomogram composed of LH, free testosterone, BMI, period times per year and the application of clomiphene may predict the ovulation among PCOS patients.

Observation on efficacy and underlying mechanism of cheek acupuncture on ovulation induction for infertile women with PCOS: Case series.

RATIONALE: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder among women of childbearing age and is the primary cause of anovulatory infertility, accounting for 70% to 80% of cases. Ovulation induction is the main treatment approach for infertile patients with PCOS. Commonly utilized medications for this purpose are clomiphene citrate (CC) and letrozole (LE). Clomiphene citrate administration results in an ovulation rate ranging from 60% to 85%, while the pregnancy rate is limited to 35% to 40%, and a further reduction is observed in live birth rates. Letrozole demonstrates a slightly higher pregnancy rate and live birth rate compared to clomiphene citrate, although challenges persist in terms of longer stimulation cycles, multiple pregnancies, and the risk of ovarian hyperstimulation syndrome (OHSS). Clinical reports indicate that acupuncture therapy shows promising efficacy in treating patients with PCOS-related infertility, despite a partially unclear understanding of its underlying mechanisms. PATIENT CONCERNS: In this study, one patient did not achieve pregnancy despite more than a year of ovulation induction using clomiphene citrate and letrozole. However, after 3 months of receiving cheek acupuncture therapy, she successfully conceived and gave birth to a liveborn baby. Another patient achieved natural conception and live birth after 2 months of exclusive cheek acupuncture therapy. DIAGNOSIS: PCOS. INTERVENTIONS: Cheek acupuncture therapy. OUTCOMES: Both of them successfully conceived and gave birth to a liveborn baby. LESSONS: These findings suggest that cheek acupuncture therapy can effectively stimulate follicle development and ovulation, potentially improving endometrial receptivity. According to holographic theory, there is a biologically holographic model within the cheek region that shares a homology with the human body structure. This model provides an explanation for the regulatory effects of cheek acupuncture point stimulation on the Hypothalamic-Pituitary-Ovarian axis (HPO), which subsequently influences follicle development and ovulation in patients. Consequently, when cheek acupuncture therapy is applied alone or in combination with ovulation induction medication, patients have the ability to achieve successful pregnancy and experience a smooth delivery.

Embryo transfer into anestrous recipient mares prepared using clomiphene citrate and short-acting progesterone.

Embryo transfer (ET) is an important technology for genetic improvement programs in the equine industry. Many protocols have been used for preparation of recipients. This study evaluates a new protocol for preparation of acyclic embryo recipient mares using clomiphene citrate (CC) and short-acting oral progesterone (Altrenogest). Seventy-two native breed recipient mares were divided into 2 groups. Group 1(G1) included 60 non-cyclic mares with follicular structures ≤ 15 mm in diameter that received CC and Altrenogest. Group 2 (G2) included 12 cyclic recipient mares that served as a control group. G1 mares were treated with oral CC at a dose of 250 mg for 4 days followed by oral administration of Altrenogest for 6 days. Ultrasonography was carried out for evaluation of uterine echotexture response to hormonal treatment, and pregnancy diagnosis post ET. Serum estradiol and progesterone concentrations were also assessed. All data were statistically analyzed. The results revealed that the serum progesterone concentrations in G1 were higher than G2 (P < 0.001). There was no difference in the estradiol concentrations between both groups during diestrus phase (P > 0.05). The pregnancy rate was higher in G1 (83.3 %) than G 2 (66.6 %). In conclusion, using oral CC and Altrenogest, as a new protocol, was effective for preparation of acyclic recipient mares in this study.

Sublingual human chorionic gonadotropin as an adjuvant to ovulation induction.

OBJECTIVE: To evaluate the efficacy of sublingually administered human chorionic gonadotropin (HCG) in combination with clomiphene citrate (CC) or letrozole (LTZ) for ovulation induction. METHODS: In this prospective, double-blind, randomized study, the patients were divided into two placebo groups and two intervention groups using CC, LTZ, and HCG. RESULTS: There were no statistically significant differences in ovulation induction between the groups. We compared endometrial thickness at the beginning of the cycle and during the pre-ovulatory period, and detected a moderately positive correlation when CC was administered with HCG. CONCLUSIONS: Sublingual HCG with CC caused a moderately positive correlation with endometrial thickening when compared with that at the beginning of the cycle and during the pre-ovulatory period. There was no significant change in the number of pre-ovulatory follicles.

Insulin-sensitizing agents for infertility treatment in woman with polycystic ovary syndrome: a narrative review of current clinical practice.

PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine, metabolic, and reproductive disorder which, according to the Rotterdam criteria, affects up to 24% of women of childbearing age. Although the prevalence of infertility in this subpopulation of women is high, the optimal treatment has not been fully established yet. Insulin resistance is considered to be an important mechanism involved in the development of PCOS; hence, the aim of this narrative review is to present an overview of the current pharmacological insulin-sensitizing treatment modalities for infertile women with PCOS. METHODS: A MEDLINE and PubMed search for the years 1990-2023 was performed using a combination of keywords. Clinical trials with insulin sensitizers used for infertility treatment as well as analyses of systematic reviews and meta-analyses were evaluated. When deemed necessary, additional articles referenced in the retrieved papers were included in this narrative review. RESULTS: Several insulin-sensitizing compounds and various therapeutical protocols are available for infertility treatment of women with PCOS. Metformin is the most common adjuvant medication to induce ovulation in infertile women with PCOS and is more frequently administered in combination with clomiphene citrate than on its own. Recently, inositol and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as possible options for infertility treatment in PCOS. CONCLUSION: The future of medical treatment of PCOS women with infertility lies in a personalized pharmacological approach, which involves various compounds with different mechanisms of action that could modify ovarian function and endometrial receptivity, ultimately leading to better overall reproductive outcomes in these women.

The burden of very early dropout in infertility care: a nationwide population-based cohort study.

STUDY QUESTION: What is the frequency and the associated factors of very early dropout following unsuccessful clomiphene citrate (CC)/gonadotropin treatment in the context of full coverage of treatment cost. SUMMARY ANSWER: Despite free treatment, almost one in four women had a very early dropout following unsuccessful CC/gonadotropin treatment, with patients below the poverty line being more likely to drop out early. WHAT IS KNOWN ALREADY: Success of infertility care is tarnished by very high dropout rates. Infertility care dropout has been considered as resulting principally from financial barriers because of the high cost of treatment. Nearly all previous work addressed dropout following IVF/ICSI. Factors associated with dropout following CC/gonadotropins may be different and also need to be investigated. STUDY DESIGN, SIZE, DURATION: Nationwide population-based cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the French national health insurance and hospital databases, we included in the cohort 27 416 women aged 18-49 years unsuccessfully treated with CC/gonadotropins in 2017. The main outcome was very early dropout, defined as discontinuation of all infertility treatment after unsuccessful treatment for 1-3 months. Very early treatment dropout was analysed by multivariate logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Among women unsuccessfully treated with CC/gonadotropins, 22% dropped out of infertility care within 3 months. In multivariate analysis, higher early dropout following unsuccessful CC/gonadotropin treatment was associated with older and younger ages (≥35 and <25 years), being below the poverty line, being treated with CC prescribed by a general practitioner and lack of infertility tests or monitoring. LIMITATIONS, REASONS FOR CAUTION: This study is based on health administrative data that do not include reasons for dropout and record only a limited amount of information. It is thus not possible to analyse the reason for early dropout. WIDER IMPLICATIONS OF THE FINDINGS: Despite full coverage of all infertility treatment, women under the poverty line have a higher risk of very early dropout following unsuccessful CC/gonadotropin treatment. Better understanding is needed of the non-financial barriers and difficulties faced by these patients. To address disparities in infertility treatment, practitioner training could be reinforced to adapt to patients from different social and cultural backgrounds. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the ANR StimHo project, grant ANR-17-CE36-0011-01 from the French Agence Nationale de la Recherche. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Antimüllerian hormone level predicts ovulation in women with polycystic ovary syndrome treated with clomiphene and metformin.

OBJECTIVE: To describe the serum anti-Müllerian hormone (AMH) concentrations in a large, well-phenotyped cohort of women with polycystic ovary syndrome (PCOS) and evaluate whether AMH predicts successful ovulation induction in women treated with clomiphene and metformin. DESIGN: Secondary analysis of randomized controlled trial. SETTING: Not applicable. PATIENT(S): A total of 333 women with anovulatory infertility attributed to PCOS who participated in the double-blind randomized trial entitled the Pregnancy in Polycystic Ovary Syndrome I (PPCOS I) study (registration number, NCT00068861) who had serum samples from baseline laboratory testing available for further serum analysis were studied. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The association between the baseline AMH levels in each of the 3 treatment groups and ovulation, pregnancy, and live birth rates were assessed. RESULT(S): A total of 322 individuals had a baseline AMH concentration available, of which the mean AMH was 11.7 ± 8.3 ng/mL (range 0.1-43.0 ng/mL). With each unit (1 ng/mL) increase in baseline AMH, the odds of ovulation decreased by 10% (odds ratio, 0.90; 95% confidence interval, 0.86-0.93); this effect did not differ by treatment group. Women with a high baseline AMH concentration (>8 ng/mL) were significantly less likely to ovulate compared with those with a normal baseline AMH concentration (<4 ng/mL) (odds ratio, 0.23; 95% confidence interval, 0.05-0.68). This remained statistically significant when controlling for confounders, including age, body mass index, time in study, and Homeostatic Model Assessment for Insulin Resistance score. Ovulation occurred even at very high AMH concentrations; there was no maximum level noted at which no ovulation events occurred. Baseline AMH concentration was not associated with pregnancy or live birth rates when controlling for confounders. CONCLUSION(S): These AMH values in well-phenotyped individuals with PCOS add to the literature and will aid in identifying AMH criteria for the diagnosis of PCOS. In women with infertility and PCOS, a higher AMH concentration was associated with reduced odds of ovulation with ovulation induction with clomiphene, clomiphene + metformin, and metformin. CLINICAL TRIAL REGISTRATION NUMBER: The original trial from which this analysis is derived was entitled "Pregnancy in Polycystic Ovary Syndrome: A 30 Week Double-Blind Randomized Trial of Clomiphene Citrate, Metformin XR, and Combined Clomiphene Citrate/Metformin XR For the Treatment of Infertility in Women With Polycystic Ovary Syndrome" and was registered on ClinicalTrials.gov as number NCT00068861. The URL for the trial is https://clinicaltrials.gov/study/NCT00068861. The first subject was enrolled in November 2002.

Meta analysis of ovulation induction effect and pregnancy outcome of acupuncture & moxibustion combined with clomiphene in patients with polycystic ovary syndrome.

Objective: Using Mesh Meta Analysis to evaluate the efficacy of Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene for treating Polycystic Ovary Syndrome (PCOS), in order to provide evidence-based medical evidence for whether to recommend Acupuncture & Moxibustion or Combine western medicine to treat PCOS. Methods: Eight databases including The Cochrane Library, Pubmed, Embase, Web of Science, CNKI, Wanfang Date, VIP and CBM were searched by computer. The included research period is from the establishment of the database to May 2023, which concerned with randomized controlled trials involving Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene on ovulation induction and pregnancy outcome in patients with PCOS. The duration of the research paper is from 2016 to 2023.The inclusion criteria refer to the Rotterdam standards issued by the European Center for Human Reproduction and Embryology and the American Society of Reproductive Medicine in January 2003, or the Expert Consensus on the Diagnosis and Treatment of Polycystic Ovarian Syndrome by the Endocrinology Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association. Simultaneously exclude related diseases, repetitive literature, as well as literature with incomplete abstract information and no original data provided. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias included in the study, using Stata17.0 software for a mesh meta-analysis. Results: Six randomized controlled trials were included, covering 1410 PCOS patients. Three interventions included Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene. Mesh Meta Analysis showed that in terms of improving ovulation rate, there was no statistical difference between Acupuncture & Moxibustion (A), Clomiphene (B), Clomiphene combined with Acupuncture & Moxibustion (C) (P>0.05).Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=0.15,95% CI (-0.51,0.80)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.60,95% CI (0.97,2.23)], Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.45,95% CI (0.91,1.99)]. In terms of pregnancy outcome, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.80,95% CI (-1.84,0.23)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=0.29,95% CI (-0.73,1.30)], and Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.09,95% CI (0.39,1.79)], The order of pregnancy rate from high to low is Acupuncture & Moxibustion combined with Clomiphene (C), Acupuncture & Moxibustion (A), Clomiphene (C).In terms of influencing endometrial thickness, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.84,95% CI (-1.87,0.19)], Acupuncture & Moxibustion (A) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=0.26,95% CI (-1.01,1.53)], Clomiphene (B) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=1.10,95% CI (0.36,1.84)], Acupuncture & Moxibustion combined with Clomiphene (C) has the best effect on improving endometrial thickness. In subgroup analysis, the effect of Acupuncture & Moxibustion treatment frequency on ovulation rate and pregnancy rate was not statistically significant. The combination of Acupuncture & Moxibustion, Electroacupuncture and warm Acupuncture & Moxibustion has no effect on the pregnancy rate, but the combination of Electroacupuncture and Clomiphene has the best effect on improving the ovulation rate. In the observation of adverse reactions, compared with clomiphene alone, Acupuncture & Moxibustion combined with Clomiphene can reduce the occurrence of Luteinized Unruptured Follicle Syndrome (LUFS) and Ovarian Hyperstimulation Syndrome (OHSS), and reduce the occurrence of physical adverse reactions such as nausea, vomiting, headache and dermatitis. Conclusion: Acupuncture & Moxibustion is effective in improving the ovulation promoting effect and pregnancy outcome of PCOS patients. The ovulation promoting effect of Acupuncture & Moxibustion or combined with Clomiphene is similar to that of Clomiphene alone, but Acupuncture & Moxibustion combined with Clomiphene has more advantages in improving the pregnancy rate of PCOS, and it also can reduce the adverse reactions of Clomiphene alone. Acupuncture & Moxibustion can be used as a recommended treatment for PCOS. More cases should also be included in the subgroup analysis to study the impact of Acupuncture & Moxibustion programs on clinical efficacy and further optimize the Acupuncture & Moxibustion treatment program. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier (CRD42023433057).

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.

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.

Letrozole in fertility treatment.

This review describes the current evidence regarding the putative indications of letrozole (LTZ) in fertility treatment. Prior to intrauterine insemination, LTZ is recommended in women with normogonadotrophic oligo-anovulation. In ovulatory women, LTZ is equal to clomiphene and may be used instead of exogenous gonadotrophin. LTZ may be used as co-treatment in poor responders prior to in vitro fertilization/intracytoplasmic sperm injection. In addition, LTZ prior to frozen-thawed embryo transfer is increasingly used in women with normogonadotrophic oligo-anovulation.

Does mid-luteal progesterone predict pregnancy in intrauterine insemination cycles following sequential clomiphene citrate and gonadotropin treatment?

This study aimed to determine whether serum mid-luteal progesterone (MLP) levels measured in the current treatment cycles of infertile women undergoing controlled ovarian hyperstimulation and intrauterine insemination following the sequential use of clomiphene citrate and gonadotropin may predict pregnancy. A total of 107 consecutive anovulatory women were included in this prospective cohort study. Patients with other causes of infertility were also excluded from the study. None of the patients received progesterone treatment for luteal phase support. The data recorded for each woman included age, body mass index, infertility type and duration, basal hormone levels, and previous and current cycle characteristics with MLP levels. Ovulation was confirmed using MLP and sonographic evaluation in all patients. An MLP level of > 3 ng/mL was regarded as a sign of ovulation. After treatment, the patients were divided into 2 groups according to the presence or absence of pregnancy, and the obtained data were compared between the groups. There were no significant differences in age, body mass index, or basal hormone levels between the 2 groups (all P > .05). However, the duration of infertility was significantly shorter in the pregnancy group (P = .003). The anovulation rate in this cohort was 18.7% (n = 20). A total of 15 (14%) were examined. MLP levels were 25.1 ± 13.8 ng/mL and 18.3 ± 14.5 ng/mL in the pregnant and nonpregnant groups, respectively (P:.089). Based on the receiver operating characteristic curve analysis, it was determined that there was no predictive value of the mid-luteal phase progesterone level for pregnancy in patients in whom ovulation was detected. Mid-luteal serum progesterone levels did not predict pregnancy in infertile women who underwent controlled ovarian hyperstimulation with sequential clomiphene citrate plus gonadotropin treatment and intrauterine insemination.

In vitro fertilisation for unexplained subfertility.

BACKGROUND: In vitro fertilisation (IVF) is a treatment for unexplained subfertility but is invasive, expensive, and associated with risks. OBJECTIVES: To evaluate the effectiveness and safety of IVF versus expectant management, unstimulated intrauterine insemination (IUI), and IUI with ovarian stimulation using gonadotropins, clomiphene citrate (CC), or letrozole in improving pregnancy outcomes. SEARCH METHODS: We searched following databases from inception to November 2021, with no language restriction: Cochrane Gynaecology and Fertility Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL. We searched reference lists of articles and conference abstracts. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing effectiveness of IVF for unexplained subfertility with expectant management, unstimulated IUI, and stimulated IUI. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. MAIN RESULTS: IVF versus expectant management (two RCTs) We are uncertain whether IVF improves live birth rate (LBR) and clinical pregnancy rate (CPR) compared to expectant management (odds ratio (OR) 22.0, 95% confidence interval (CI) 2.56 to 189.37; 1 RCT; 51 women; very low-quality evidence; OR 3.24, 95% CI 1.07 to 9.8; 2 RCTs; 86 women; I2 = 80%; very low-quality evidence). Adverse effects were not reported. Assuming 4% LBR and 12% CPR with expectant management, these would be 8.8% to 9% and 13% to 58% with IVF. IVF versus unstimulated IUI (two RCTs) IVF may improve LBR compared to unstimulated IUI (OR 2.47, 95% CI 1.19 to 5.12; 2 RCTs; 156 women; I2 = 60%; low-quality evidence). We are uncertain whether there is a difference between IVF and IUI for multiple pregnancy rate (MPR) (OR 1.03, 95% CI 0.04 to 27.29; 1 RCT; 43 women; very low-quality evidence) and miscarriage rate (OR 1.72, 95% CI 0.14 to 21.25; 1 RCT; 43 women; very low-quality evidence). No study reported ovarian hyperstimulation syndrome (OHSS). Assuming 16% LBR, 3% MPR, and 6% miscarriage rate with unstimulated IUI, these outcomes would be 18.5% to 49%, 0.1% to 46%, and 0.9% to 58% with IVF. IVF versus IUI + ovarian stimulation with gonadotropins (6 RCTs), CC (1 RCT), or letrozole (no RCTs) Stratified analysis was based on pretreatment status. Treatment-naive women There may be little or no difference in LBR between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 1.19, 95% CI 0.87 to 1.61; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 1.63, 95% CI 0.91 to 2.92; 2 RCTs; 221 women; I2 = 54%; low-quality evidence); or between IVF and IUI + CC (OR 2.51, 95% CI 0.96 to 6.55; 1 RCT; 103 women; low-quality evidence). Assuming 42% LBR with IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles) and 26% LBR with IUI + gonadotropins (1 IVF to 1 IUI cycle), LBR would be 39% to 54% and 24% to 51% with IVF. Assuming 15% LBR with IUI + CC, LBR would be 15% to 54% with IVF. There may be little or no difference in CPR between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 1.17, 95% CI 0.85 to 1.59; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 4.59, 95% CI 1.86 to 11.35; 1 RCT; 103 women; low-quality evidence); or between IVF and IUI + CC (OR 3.58, 95% CI 1.51 to 8.49; 1 RCT; 103 women; low-quality evidence). Assuming 48% CPR with IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles) and 17% with IUI + gonadotropins (1 IVF to 1 IUI cycle), CPR would be 44% to 60% and 28% to 70% with IVF. Assuming 21% CPR with IUI + CC, CPR would be 29% to 69% with IVF. There may be little or no difference in multiple pregnancy rate (MPR) between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 0.82, 95% CI 0.38 to 1.77; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 0.76, 95% CI 0.36 to 1.58; 2 RCTs; 221 women; I2 = 0%; low-quality evidence); or between IVF and IUI + CC (OR 0.64, 95% CI 0.17 to 2.41; 1 RCT; 102 women; low-quality evidence). We are uncertain if there is a difference in OHSS between IVF and IUI + gonadotropins with 1 IVF to 2 to 3 IUI cycles (OR 6.86, 95% CI 0.35 to 134.59; 1 RCT; 207 women; very low-quality evidence); and there may be little or no difference in OHSS with 1 IVF to 1 IUI cycle (OR 1.22, 95% CI 0.36 to 4.16; 2 RCTs; 221 women; I2 = 0%; low-quality evidence). There may be little or no difference between IVF and IUI + CC (OR 1.53, 95% CI 0.24 to 9.57; 1 RCT; 102 women; low-quality evidence). We are uncertain if there is a difference in miscarriage rate between IVF and IUI + gonadotropins with 1 IVF to 2 to 3 IUI cycles (OR 0.31, 95% CI 0.03 to 3.04; 1 RCT; 207 women; very low-quality evidence); and there may be little or no difference with 1 IVF to 1 IUI cycle (OR 1.16, 95% CI 0.44 to 3.02; 1 RCT; 103 women; low-quality evidence). There may be little or no difference between IVF and IUI + CC (OR 1.48, 95% CI 0.54 to 4.05; 1 RCT; 102 women; low-quality evidence). In women pretreated with IUI + CC IVF may improve LBR compared with IUI + gonadotropins (OR 3.90, 95% CI 2.32 to 6.57; 1 RCT; 280 women; low-quality evidence). Assuming 22% LBR with IUI + gonadotropins, LBR would be 39% to 65% with IVF. IVF may improve CPR compared with IUI + gonadotropins (OR 14.13, 95% CI 7.57 to 26.38; 1 RCT; 280 women; low-quality evidence). Assuming 30% CPR with IUI + gonadotropins, CPR would be 76% to 92% with IVF. AUTHORS' CONCLUSIONS: IVF may improve LBR over unstimulated IUI. Data should be interpreted with caution as overall evidence quality was low.

Comparing efficacy and safety of stair step protocols for clomiphene citrate and letrozole in ovulation induction for women with polycystic ovary syndrome (PCOS): a randomized controlled clinical trial.

Polycystic ovary syndrome (PCOS) is characterized by menstrual irregularities, high androgen levels, and ovarian cysts. Clomiphene citrate (Clomid) and letrozole have both been investigated as ovulation induction therapies for PCOS. This interventional study aimed to compare the efficacy and safety of a stairstep practice of letrozole versus clomiphene citrate in women with PCOS. A total of 100 women diagnosed with PCOS and infertility participated in the study, which took place from March 2021 to July 2022 at the Maternity and Children Teaching Hospital in Adiwaniyah Province, Iraq. Participants were randomly assigned to one of two groups (each with 50 women): the first group received clomiphene citrate in a stair step pattern (single dose of 50 mg, 100 mg, and 150 mg) for five days, for a maximum of three cycles; the second group received letrozole in a stair step pattern (single dose of 2.5, 5, and 7.5 mg) for five days, for a maximum of three cycles. Follicle size was monitored using ultrasound to achieve a follicle size >18 mm. The ovulation rate was higher in the letrozole group (86.0%) compared to the clomiphene citrate group (72.0%), although the difference was not statistically significant (p=0.086). The pregnancy rate was slightly higher in the letrozole group (22.0% vs 18.0%), but also not statistically significant (p=0.617). However, the mean time from menstruation to ovulation was significantly shorter in the letrozole group (17.20±1.32 days) compared to the clomiphene citrate group (24.08 ± 1.56 days, p<0.001). There were no significant differences in common side effects between the two groups. Overall, letrozole was found to be as safe as clomiphene citrate but demonstrated a shorter time to ovulation. Further studies with larger sample sizes are necessary to validate these findings and determine their clinical implications.

The efficacy of Fuke Qianjin tablets combined with clomiphene citrate on infertility patients with polycystic ovary syndrome: A retrospective analysis.

PURPOSE: Clinical efficacy of Fuke Qianjin tablets combined with clomiphene citrate on infertility patients with polycystic ovary syndrome (PCOS) was expected to be retrospectively analyzed in this study. METHODS: In this paper, 100 infertility patients with PCOS were selected and divided into the observation and control groups based on different medications. Firstly, clinical data of both groups of patients were acquired. Then, the uterine receptivity and ovarian status, the levels of sex hormones, inflammation and oxidative stress, and the pregnancy outcomes between the 2 groups were compared and analyzed before and after treatment. RESULTS: After a variety of comparisons and analyses, Fuke Qianjin tablets combined with clomiphene citrate were confirmed to improve the uterine receptivity and ovarian status, levels of sex hormone, inflammation and oxidative stress, and pregnancy outcomes in infertility patients with PCOS. CONCLUSIONS: Overall, Fuke Qianjin tablets + clomiphene citrate treatment shows good clinical efficacy and is worth promotion in clinical practice.

Comparative Study Of Combined Co-Enzyme Q10 And Clomiphene Citrate Vs Clomiphene Citrate Alone For Ovulation Induction In Patients With Polycystic Ovarian Syndrome.

A total of 136 patients with PCOS were followed through the Department of the Obstetrics and Gynaecology, Unit-IV, Lady Aitchison Hospital, Lahore. Patients were randomly divided by lottery method into two groups i.e., Group-A (CoQ10 plus Clomiphene citrate) and Group-B (Clomiphene citrate alone). The selected patients in the study group (group-A) were given Clomiphene citrate 100mg/day from cycle days 2-6 for 45 days (2 cycles) and CoQ10 in a dose of 50mg soft gel capsules thrice per day starting at cycle day-2, until HCG administration. Patients in controlled group (group 21 B) received Clomiphene citrate 100mg/day twice a day cycle for 45 days. Data were analysed in SPSS v25.0. In group-A (CoQ10 plus Clomiphene citrate), successful ovulation induction was noted in 16 (23.5%) patients, showing that with the addition of CoQ10, the chances of ovulation induction increased.

Intrauterine Insemination After Human Chorionic Gonadotropin Trigger or Luteinizing Hormone Surge: A Meta-analysis.

OBJECTIVE: To assess the odds of pregnancy after intrauterine insemination (IUI) timed by ultrasound monitoring and human chorionic gonadotropin (hCG) administration compared with monitoring luteinizing hormone (LH) levels. DATA SOURCES: We searched PubMed (MEDLINE), EMBASE (Elsevier), Scopus (Elsevier), Web of Science (Clarivate Analytics), ClinicalTrials.gov (National Institutes of Health), and the Cochrane Library (Wiley) from the inception until October 1, 2022. No language limitations were applied. METHODS OF STUDY SELECTION: After deduplication, 3,607 unique citations were subjected to blinded independent review by three investigators. Thirteen studies (five retrospective cohort, four cross-sectional, two randomized controlled trials, and two randomized crossover studies) that enrolled women undergoing natural cycle, oral medication (clomid or letrozole), or both for IUI were included in the final random-effects model meta-analysis. Methodologic quality of included studies was assessed with the Downs and Black checklist. TABULATION, INTEGRATION, AND RESULTS: Data extraction was compiled by two authors, including publication information, hCG and LH monitoring guidelines, and pregnancy outcomes. No significant difference in odds of pregnancy between hCG administration and endogenous LH monitoring was observed (odds ratio [OR] 0.92, 95% CI 0.69-1.22, P =.53). Subgroup analysis of the five studies that included natural cycle IUI outcomes also showed no significant difference in odds of pregnancy between the two methods (OR 0.88, 95% CI 0.46-1.69, P =.61). Finally, a subgroup analysis of 10 studies that included women who underwent ovarian stimulation with oral medications (clomid or letrozole) did not demonstrate a difference in odds of pregnancy between ultrasonography with hCG trigger and LH-timed IUI (OR 0.88, 95% CI 0.66-1.16, P =.32). Statistically significant heterogeneity was noted between studies. CONCLUSION: This meta-analysis showed no difference between pregnancy outcomes between at-home LH monitoring and timed IUI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021230520.

Oral sildenafil citrate: a potential approach for improvement of endometrial thickness and treatment of unexplained infertility in women.

OBJECTIVE: The study aimed to determine the impact of using sildenafil citrate as an adjuvant with clomiphene citrate (CC) in the treatment of women with unexplained infertility. PATIENTS AND METHODS: 130 women with unexplained infertility were enrolled in a prospective randomized study. After dividing into two groups, all patients received CC 50 mg-BD from the 2nd to the 7th day of the cycle. Oral sildenafil citrate 20 mg was given BD to the study group from the end of menstruation till ovulation. A transvaginal ultrasound was carried out for all patients to assess ovulation, number of follicles, and endometrial thickness (ET). The beta-hCG blood test was used to determine pregnancy two weeks after ovulation followed by an ultrasound to confirm viability. Adverse effects were recorded and miscarriage, ectopic, and multi-fetal pregnancy were followed up for twelve weeks. RESULTS: Median ET in the study group was 8 mm compared to 7 mm in the control group (p<0.01). The number of pregnancies increased in the study group but with no significant difference. The median ET was greater in the study group with an infertility duration of less than 2 years. Headache was the most significant adverse effect in the study group (9.2% vs. 1.5%, p=0.052). CONCLUSIONS: Adding sildenafil citrate to CC is a good choice for overcoming the antiestrogenic action of CC and improving ET in women with unexplained infertility, especially in those with less than 2 years of infertility.

Modulatory properties of Thespesia garckeana (F. Hoffm.) Exell & Hillc. Aqueous fruit extract on female rats reproductive hormones and tissues histology and potential inhibitory activity of its constituents against SRD5α2.

ETHNOPHARMACOLOGICAL RELEVANCE: Thespesia garckeana (F. Hoffm.) Exell & Hillc. is called Gorontula (Kola of Tula) in Nigeria, Morojwa in Bostwana, and Thespesia garckeana in South Africa and is widely distributed across Africa. Its parts reportedly possess multiple medicinal properties and are employed for treating various diseases. In Tula, Gombe State, Nigeria, the ripe fruit decoction is taken as remedy for female infertility as documented by Ochokwu and co in the Journal of Biology, Agriculture and Healthcare in 2015. AIM OF THE STUDY: This research examined the effects of aqueous fruit extract of T. garckeana (F. Hoffm.) Exell & Hillc. (AFETG) on selected reproductive tissues and hormones in female rats and also evaluated the inhibitory potentials of its phytoconstituents against human 5-alpha reductase 2 (SRD5α2) using in silico approach. METHODS: Twenty-five (25) sexually matured female rats were randomized into 5 groups (i.e. A - E). Oestrous in the rats was synchronized (subcutaneous oestradiol conjugate [10 µg/100 g BW]). Group A received distilled water (control). Group B received standard drug, clomiphene citrate (0.85 mg/kg BW), while groups C, D, and E received AFETG at 50, 100, and 200 mg/kg BW respectively. The animals were treated for five (5) days and sacrificed 24 h after. Their blood was collected and prepared for analysis of serum prolactin, oestradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) while ovaries, uteruses, and oviducts were studied for histological and histomorphometric changes. For the in silico study, the target protein, human steroid 5α-reductase 2 (SRD5α2) was prepared and its receptor grid was generated using Optimized Potential for Liquid Simulations-2005. The ligand 2D structures were prepared using LigPrep 2.4 software and docked using Glide. The binding energy of the ligands to the protein receptor was predicted using Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis. RESULTS: AFETG significantly increased serum levels of E2 but did not alter serum levels of prolactin, LH and FSH when compared with distilled water and clomiphene citrate. AFETG also significantly increased ovarian tertiary follicular diameter, oviductal epithelial height and serosa thickness as well as uterine endometrial epithelial height, endometrial thickness, and myometrial thickness when compared with control. Ovarian secondary follicular diameter and oviductal submucosa thickness and muscular thickness were significantly decreased by AFETG when compared with control. Two compounds in T. garckeana (F. Hoffm.) Exell & Hillc.; D-Melezitose (-12.55 kcal/mol XP GScore) and 1, 3, 4-trihydroxy-5-oxo cyclohexane-1-carboxylic acid (-9.136 kcal/mol XP GScore) exhibited higher binding affinities for SRD5α2 than the reference ligand, epristeride (-8.096 kcal/mol XP GScore). In conclusion, the ability of AFETG to increase serum E2 level, thickness of uterine endometrium and ovarian tertiary follicles size can be explored for the treatment of female infertility caused by thinning of the uterine endometrium and reduced follicular size. Two compounds in AFETG (i.e. D-Melezitose and 1, 3, 4-trihydroxy-5-oxo cyclohexane-1-carboxylic acid are potential inhibitors of SRD5α2, thus aiding the biosynthesis of E2. Available evidence therefore corroborate the traditional use of T. garckeana (F. Hoffm.) Exell & Hillc fruit as a female fertility enhancer in Northern Nigeria.