Low prolactin levels are associated with an increased risk of vascular and metabolic diseases. Women with prolactin deficiency appear to have attenuated responses to lipid-lowering and insulin-sensitizing medications. This study aimed to evaluate the impact of hypoprolactinemia on the cardiometabolic effects of rosuvastatin in men. Three groups of men with indications for statin therapy were included. Group 1 comprised 16 individuals with prolactin levels below 3 ng/mL, while groups 2 (n = 23) and 3 (n = 37) included patients with levels between 3 and 20 ng/mL. Participants in groups 1 and 2 were chronically treated with cabergoline. Throughout the six-month study period, all patients received rosuvastatin. In addition to lipid profile and prolactin levels, assessed parameters included high-sensitivity C-reactive protein (hs-CRP), fibrinogen, homocysteine, uric acid, urinary albumin-to-creatinine ratio (UACR), carbohydrate metabolism markers, testosterone, and carotid intima-media thickness (CIMT). At baseline, men with hypoprolactinemia showed higher hs-CRP, fibrinogen, homocysteine, UACR, HbA1c, and HOMA-IR, and lower testosterone than those with normal prolactin levels. Rosuvastatin reduced total and LDL cholesterol in all groups, with a greater effect in groups 2 and 3. Reductions in hs-CRP, fibrinogen, uric acid, homocysteine, and UACR occurred only in groups with normal prolactin. Group 1 exhibited increases in HbA1c and HOMA-IR. At study end, CIMT was greater in group 1 than in groups 2 and 3, whereas the latter two groups had comparable values. In men with hypoprolactinemia, the effects of rosuvastatin on total and LDL cholesterol, hs-CRP, fibrinogen, uric acid, homocysteine, UACR, HbA1c, HOMA-IR, and CIMT correlated with baseline and posttreatment prolactin concentrations. These findings suggest that hypoprolactinemia may worsen cardiometabolic outcomes in men receiving rosuvastatin therapy.
Chronic endometritis is linked to recurrent pregnancy loss and in vitro fertilization failure. The responsiveness to antibiotics suggests a bacterial cause, however endometriosis could also play a role. This study aimed to compare treatment responses to antibiotics of patients with and without endometriosis to find out if endometriosis-related immune changes affect treatment success. We included 92 infertile women with chronic endometritis in the study. Endometriosis was staged via laparoscopy according to the revised American Society for Reproductive Medicine, adenomyosis was defined using transvaginal ultrasound. All patients were reassessed via Pipelle® after oral doxycycline treatment. The main outcome parameter was the number of CD138 positive plasma cells per 20 high-power fields before and after doxycycline. In the univariable analysis, the presence of endometriosis (odds ratio, OR 2.893; p = 0.026) and adenomyosis (OR 10.277; p < 0.001) was associated with a higher risk of persistent chronic endometritis after doxycycline, whereas in the multivariable model, the presence of adenomyosis (OR, 18.393; p < 0.001) and the baseline number of plasma cells (OR 1.371; p = 0.026) remained statistically significant. Endometriosis and adenomyosis are risks for persistent chronic endometritis after doxycycline treatment. This could support the hypothesis that affected women could have heterogeneous endometrial immunological processes.
Background/Objective: Ovarian hyperstimulation syndrome (OHSS) is a severe complication during controlled ovarian hyperstimulation. Ascites and consecutive hemoconcentration may lead to potentially life-threatening complications like thromboembolic events and the need for intensive care. The use of diuretics is widely used to treat ascites in non-OHSS patients. The aim of this study was to assess whether the use of furosemide in the treatment of OHSS was associated with a higher rate of complications compared to the literature. Methods: In this retrospective cohort study, 502 cases treated from January 2005 to June 2023 for OHSS at the Medical University of Vienna were evaluated regarding the distribution of OHSS severity, average duration of treatment, types and frequency of complications associated with antidiuretic treatment, and predictive factors for paracentesis. Results: The median AMH levels were 5.7 ng/mL. An antagonist protocol was used in 80% of stimulations. Human Chorionic Gonadotropin trigger was used in 80% of stimulations, with 71.7% of cases being early-onset. The incidence dropped from 8.4% (2006 to 2016) to 3.3% (from 2015 to 2023). The median duration of inpatient treatment was seven days, with about 75% of patients receiving furosemide as a diuretic treatment. Ascites drainage was necessary in 27.9%. None of our patients developed a thromboembolic complication following the furosemide treatment. Conclusions: During the study period, the incidence of OHSS declined, most probably as a result of advances in ovarian stimulation protocols and freezing strategies. In moderate to severe OHSS, standardized diuretic treatment with furosemide was not associated with additional thromboembolic complications as long as patients remain normovolemic.
OBJECTIVE:Up to 50% of women with functional hypothalamic amenorrhea (FHA) exhibit polycystic ovarian morphology (PCOM) on ultrasound. We aimed to compare the hormonal response to ovulation induction with pulsatile GnRH therapy in FHA patients with and without PCOM. METHODS:In this single-center observational study, 41 patients with FHA underwent 3 months of pulsatile GnRH therapy to induce ovulation. Patients were categorized into a PCOM group (n = 24) and a non-PCOM group (n = 17). Serum levels of Anti-Muellerian-hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, sex hormone-binding globulin (SHBG), testosterone, and thyroid-stimulating hormone (TSH) were assessed at baseline and after 3 months of treatment. RESULTS:At baseline, median AMH levels were significantly higher in the PCOM group (6.21 ng/ml [IQR 4.03-8.87]) compared to the non-PCOM group (1.7 ng/ml [IQR 1.14-2.20]; p < 0.001). After 3 months of pulsatile GnRH therapy, AMH levels significantly increased in the non-PCOM group (1.94 [IQR 1.39-2.49], p < 0.001), whereas no significant change was observed in the PCOM group (p = 0.218). LH, FSH, and estradiol levels increased in both groups. Pulsatile GnRH therapy effectively induced ovulation (1 dominant follicle in each patient), irrespective of ovarian morphology. CONCLUSION:The significant AMH rise in women with FHA without PCOM likely reflects restored folliculogenesis. In contrast, the absence of an AMH rise in the PCOM group was expected, given their already elevated baseline levels. Importantly, these findings suggest that pulsatile GnRH therapy does not exacerbate AMH levels in most patients.
OBJECTIVE:Women with Turner syndrome (TS) are at increased risk of reduced bone mineral density (BMD) due to primary ovarian insufficiency. This study aimed to assess longitudinal changes in BMD in TS patients receiving oral or transdermal hormone replacement therapy (HRT) and to identify factors associated with bone density decline. METHODS:This retrospective pilot study included 40 TS patients treated with oral or transdermal estradiol. The median age was 22 years in both the transdermal (20-30) and oral (20-27) groups. Median BMI was 23.1 (21.1-25.5) and 25.4 (22.1-29.1), respectively. Dual-energy X-ray absorptiometry (DEXA) of the lumbar spine and femoral neck was performed at baseline and follow-up. The primary outcome was the t-score at both sites. Univariable and multivariable logistic regression analyses were used to identify factors associated with declining t-scores. RESULTS:At baseline, 38.3% of patients had osteopenia, and 3.3% had osteoporosis. During follow-up, a decline in t-scores at at-least one skeletal site was observed in 47.5% of patients. No significant differences were found between oral and transdermal estradiol therapy regarding absolute t-scores, t-score changes, or the proportion of patients with declining t-scores (all p > 0.05). In multivariable analysis, lower vitamin D levels at follow-up were independently associated with declining t-scores. CONCLUSIONS:In TS patients, the route of estradiol administration did not significantly affect long-term BMD outcomes. Despite HRT, a substantial proportion of patients experienced bone loss. Vitamin D status has emerged as the most relevant modifiable factor associated with declining BMD, highlighting the need for bone health management beyond HRT.
BACKGROUND/OBJECTIVES:Minipuberty is a transient activation of the hypothalamic-pituitary-gonadal axis in infancy that contributes to the postnatal development of sexual organs. Its course has been shown to be influenced by maternal hypothyroidism. This study aimed to evaluate the reproductive axis and genital development in infant girls born to women with euthyroid autoimmune thyroiditis. METHODS:The study involved three groups of infants: two groups were daughters of euthyroid women with autoimmune thyroiditis, while the third group (control) consisted of daughters of women without thyroid disease during pregnancy. Half of the mothers with thyroiditis received additional vitamin D and selenium supplementation during pregnancy, whereas the other half did not. During the first 18 months of life, periodic assessments were conducted of gonadotropin concentrations in urine, as well as salivary levels of estradiol, progesterone, testosterone, androstenedione, and DHEA-S. Additionally, ovarian volume, uterine length, and breast diameter were measured in the infants. RESULTS:Daughters of women with autoimmune thyroiditis who did not receive supplementation during pregnancy exhibited lower levels of LH, estradiol, and progesterone, as well as a more rapid decline in LH and estradiol to below detectable levels, compared with daughters of healthy women. These hormonal differences were accompanied by smaller uterine length and breast diameter in this group. No differences were observed between the offspring of non-supplemented women with thyroiditis and daughters of healthy women regarding the levels of other hormones or ovarian volume. The dynamics of all assessed hormone levels and organ measurements did not differ between daughters of euthyroid women with thyroiditis who received vitamin D and selenium supplementation and daughters of healthy women. LH and progesterone levels showed inverse correlations with anti-thyroid peroxidase antibody titers, whereas uterine and breast dimensions positively correlated with estradiol levels. CONCLUSIONS:These findings suggest that maternal euthyroid autoimmune thyroiditis can affect the progression of female minipuberty, while supplementation with vitamin D and selenium during pregnancy may mitigate this effect.
Oxidative stress appears to be implicated in both the initiation and progression of autoimmune thyroiditis. Selenomethionine, which exhibits antioxidant properties, has been shown to reduce thyroid antibody titers in patients with autoimmune thyroiditis. Recent evidence suggests that vitamin E, a fat-soluble antioxidant, may protect against the development of autoimmune thyroiditis, and that its supplementation has been associated with improvements in female sexual function. The objective of the present pilot study was to determine whether vitamin E intake modulates the effects of selenomethionine on female sexual function and depressive symptoms in individuals with thyroid autoimmunity. The study enrolled three groups of reproductive-age women with euthyroid autoimmune thyroiditis, with 26 participants in each group. The groups were matched for age, thyroid peroxidase antibody titers, and TSH levels and differed according to vitamin E intake: adequate intake (group A), low intake (group B), and high intake (group C). All participants received selenomethionine supplementation (200 µg/day) for six months. Antibody titers and hormone levels were measured, and participants completed questionnaires assessing female sexual function (FSFI) and depressive symptoms (BDI-II). At baseline, no differences in biochemical outcomes were observed between the groups, except for testosterone levels. The study groups differed in sexual desire and arousal domain scores, which were higher in group A than in the other two groups. Total FSFI scores, the remaining FSFI domain scores, and BDI-II scores did not differ between groups at baseline. Across all groups, selenomethionine reduced thyroid peroxidase and thyroglobulin antibody titers and increased SPINA-GD and the ratio of free triiodothyronine to free thyroxine; however, the effects on antibody titers were most pronounced in group A. An increase in SPINA-GT and testosterone levels following selenomethionine supplementation was observed only in group A. In this group, selenomethionine also led to significant improvements in total FSFI scores and all individual domain scores. In contrast, in the remaining groups, the effects of supplementation were limited to increases in domain scores for lubrication, sexual satisfaction, and pain. A treatment-related reduction in total BDI-II scores was observed exclusively in women with adequate vitamin E intake. These findings suggest, for the first time, that dietary intake of a natural antioxidant may influence the effects of exogenous selenomethionine on sexual function and depressive symptoms in reproductive-age women with euthyroid autoimmune thyroiditis.
Background/Objectives: Low vitamin D status was found to attenuate the impact of metformin on circulating levels of anterior pituitary hormones, but this inhibitory effect was absent in vitamin D-repleted subjects. No previous study investigated the interaction between metformin and exogenous vitamin D at the pituitary levels in individuals with normal vitamin D status. Methods: Our pilot, single-center, prospective, matched-cohort study enrolled 59 postmenopausal women with subclinical hypothyroidism and 25-hydroxyvitamin D levels in the range between 75 and 150 nmol/L. For the following six months, all the participants were treated with either metformin/vitamin D combination therapy (group 1, n = 27) or metformin alone (group 2, n = 32). The outcomes of interest included 25-hydroxyvitamin D, fasting glucose, HOMA-IR, HbA1c, TSH, FSH, LH, prolactin, ACTH, free thyroid hormones, estradiol and IGF-1. A parallel study investigated the impact of vitamin D monotherapy on the outcome measures in insulin-resistant women meeting the remaining inclusion criteria. Results: No differences in baseline biomarker values were observed between groups 1 and 2. Ninety-three percent of the patients completed the study. The increase in 25-hydroxyvitamin D levels was observed exclusively in group 1. Although glucose homeostasis markers and post-treatment levels of TSH and FSH were lower at the end of the study than at baseline in both groups, the effect of treatment was more pronounced in group 1 than in group 2. Metformin/vitamin D combination therapy, but not metformin alone, reduced LH and prolactin levels. In both groups, the TSH- and gonadotropin-lowering effects of metformin correlated with baseline levels of these pituitary hormones. Levels of ACTH, free thyroxine, free triiodothyronine, estradiol and IGF-1 remained stable throughout the study. The effects of vitamin D monotherapy were confined to an increase in plasma 25-hydroxyvitamin D concentrations and a modest enhancement in insulin sensitivity. Conclusions: Exogenous vitamin D potentiates the pituitary effects of metformin in postmenopausal women with subclinical hypothyroidism.
Euthyroid autoimmune thyroiditis (Hashimoto’s disease) has been shown to negatively affect female sexual health; however, this adverse impact appears to be mitigated by vitamin D therapy. Emerging research suggests that vitamin E may reduce susceptibility to autoimmune thyroiditis and that supplementation could contribute to improved sexual health outcomes. The present study aimed to investigate whether vitamin E status influences the effects of exogenous vitamin D on female sexual function and depressive symptoms in individuals with this condition. This pilot study included three cohorts of young women with Hashimoto’s disease, matched for age, thyroid antibody titers, and 25-hydroxyvitamin D levels, all exhibiting normal TSH and free thyroid hormone concentrations. The cohorts differed in vitamin E intake: below the recommended daily allowance (group 1), adequate intake (group 2), and high intake (exceeding 400 IU daily; group 3). All participants received vitamin D at a daily dose of 100 µg for six months. Serum hormone levels, thyroid antibody titers, and calculated indices of thyroid homeostasis were evaluated at enrollment and at the conclusion of the study. Female sexual function and depressive symptoms were also evaluated at both time points using validated instruments: the Female Sexual Function Index (FSFI) and the Beck Depression Inventory-II (BDI-II). At enrollment, group 2 scored higher than the other cohorts in the sexual desire and arousal domains. Vitamin D supplementation increased serum 25-hydroxyvitamin D in all groups. The decrease in antibody titers was most pronounced in group 2, and only in this group did vitamin D enhance thyroid secretory capacity and increase testosterone levels. In group 2, treatment led to improvements across all FSFI domains and the total score. In group 1, positive effects were limited to the lubrication and lack of pain/discomfort domains, whereas group 3 showed no changes in sexual function. Improvements in female sexual function correlated with vitamin E intake, reductions in antibody titers, and increases in testosterone levels. Significant improvements in depressive symptoms, as measured by the BDI-II, were observed exclusively in group 2. Adequate vitamin E intake is essential to achieve the full effects of vitamin D on female sexual function and mood in young euthyroid patients with Hashimoto’s disease.
Background: Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) characterized by various clinical symptoms including abdominal pain, diarrhea, fatigue, and extraintestinal manifestations, which negatively affect a patient’s quality of life. Both mainly occur in adolescence and young adulthood and therefore affect women in their sexually active period. The aim of this study was to assess the effect of IBD on female sexuality and attitudes towards contraception. Methods: A prospective cross-sectional survey study was conducted at the Medical University of Vienna, Austria. Data were collected using a self-designed questionnaire, which included questions on demographics, gynecological patient history, contraceptive choices, and fertility, as well as the Female Sexual Functionality Index (FSFI). Results: A total of 83 female patients with IBD (CD: n = 47, UC: n = 36) and 340 healthy control participants between the ages of 18 and 50 years were investigated. Demographic parameters did not differ between the groups; however, mean FSFI scores were significantly lower in the patient group (p < 0.001). Significantly fewer patients in the IBD group used contraception (p = 0.008). No significant differences regarding conception rates and infertility rates were noted between patients with IBD and control participants (p = 0.533 and p = 0.506, respectively). Conclusions: Female sexuality is significantly impaired in patients with IBD. Women with IBD do not receive sufficient information regarding contraception and should be screened for sexual dysfunction to optimize their quality of life.
Fibroids are the most common gynecological pathology in reproductive aged women and contribute to 2–3
Nearly 50% of women with functional hypothalamic amenorrhea (FHA) reveal polycystic ovarian morphology (PCOM), a known risk factor for ovarian hyperstimulation syndrome. However, gonadotropin releasing hormone-agonist (GnRH-a) triggers are not recommended in FHA, since an inadequate endogenous surge in luteinizing hormone (LH) is expected. We aimed to challenge this concept and evaluated LH levels after GnRH stimulation in FHA-women with and without PCOM. In a retrospective cohort study, 82 women with FHA, who underwent a GnRH stimulation test, were included. Thirty-five women revealed PCOM (42.7%). Twenty minutes after GnRH stimulation, there was an increase of serum LH levels in FHA-PCOM (median basal: 2.7 mIU/mL, IQR 1.1-4.6 versus median stimulated: 13.5 mIU/mL, IQR 7.8-21.6, p < 0.001) and in FHA-nonPCOM patients (median basal: 2.5 mIU/mL, IQR 0.5-3.9 versus median stimulated: 5.7 mIU/mL, IQR 2.4-13.9, p < 0.001). Overall, positive correlations (p < 0.001) were found between basal and stimulated LH levels. In FHA-PCOM patients, 42.9% of patients revealed stimulated LH levels >15 mIU/mL, while this was the case in 19.1% of FHA-nonPCOM patients (p = 0.034). In women with FHA-PCOM, ovulation induction with a GnRH-a trigger might be feasible. Future research should focus on the prediction of an adequate response to GnRH triggers in the IVF setting.
Subnormal prolactin concentrations were found to be associated with increased risk of metabolic complications. Thus, many patients with prolactin deficiency may be candidates for treatment with insulin-sensitizing drugs. The aim of this pilot prospective cohort study was to investigate metformin action on cardiometabolic risk factors in women with iatrogenic hypoprolactinemia. The study included three groups of reproductive-age women (18–50 years old) with recently diagnosed prediabetes or type 2 diabetes: 18 women with cabergoline-induced hypoprolactinemia (prolactin below 5 ng/mL) [group A], 19 normoprolactinemic women receiving cabergoline treatment because of previous prolactin excess [group B] and 25 cabergoline-naïve women with prolactin levels within the reference range [group C]. The groups were matched for age, fasting glucose and insulin sensitivity. All participants were treated with metformin for the following six months. The outcomes of interest included: glucose homeostasis markers, prolactin, testosterone, plasma lipids, concentrations of uric acid, high-sensitivity C-reactive protein [hsCRP], homocysteine and fibrinogen, and the urinary albumin-to-creatinine ratio [UACR]. Fifty-eight patients (17 in group A, 18 in group B and 23 in group C) completed the study. There were no statistical differences between groups A and B in cabergoline dose (1.19 ± 0.52 mg vs. 1.05 ± 0.46 mg weekly), cabergoline treatment duration (43 ± 12 vs. 47 ± 14 weeks), and long-term glycemic control (HbA1c in the range between 6.4 ± 0.5
New international recommendations on the diagnosis and treatment of polycystic ovary syndrome (PCOS) were published in autumn 2023 [...]
Almost half of patients with functional hypothalamic amenorrhea (FHA) show polycystic ovarian morphology (PCOM) on the ultrasound, which leads to a diagnostic confusion. Although FHA and polycystic ovarian syndrome (PCOS) have been thought to co-exist and some FHA-patients seem to have had PCOS before developing FHA, respectively, once hypothalamic inhibition proceeds, the FHA phenotype predominates over the PCOS features, except from PCOM. This connection has never been shown longitudinally. Furthermore, it is still not clear if FHA-PCOM is actually related to preexisting PCOS or if these women constitute their very own heterogeneous subgroup. Thus, the aims of this study were to evaluate changes in hormonal parameters and PCOM after remission and to provide further insight into pathophysiological processes of PCOM in FHA. Monocentric retrospective cohort study. Sixty women with FHA in remission were included. While anti-mullerian hormone (AMH) was the main outcome parameter, we also analyzed total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), sex hormone-binding globulin (SHBG) and dehydroepiandrosterone sulfate (DHEAS). PCOM was diagnosed using ultrasound. At baseline, FHA-PCOM patients revealed higher baseline prolactin (p = 0.029) and AMH levels (p < 0.001). At follow-up, compared to women without PCOM, these women had higher PCOM prevalence (48.1
IntroductionPolycystic ovary syndrome (PCOS) is often associated with insulin resistance (IR). The role of prolactin (PRL) in this context remains unclear, particularly across different PCOS phenotypes. The aim of this study was to investigate the distribution of PRL, as well as its correlation with basal IR in women with PCOS.Methods200 women with PCOS, evenly distributed across phenotypes A-D and matched for age and body mass index (BMI) were retrospectively analyzed. PRL, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), sexual hormone binding globulin (SHBG), testosterone, and BMI were assessed. Correlation analysis and unsupervised clustering (based on PRL and HOMA-IR) were performed.ResultsPRL levels were similar across phenotypes, but phenotype D had a significantly lower prevalence of HOMA-IR ≥ 2.5 (p = 0.032). PRL was inversely correlated with HOMA-IR in all groups (p < 0.05). Cluster analysis identified three distinct subgroups, independent of phenotype, differing significantly in both PRL and HOMA-IR.ConclusionPRL is inversely associated with IR in PCOS, regardless of phenotype. Cluster analysis reveals metabolic subtypes not captured by current phenotype-based classification, suggesting potential for improved risk stratification.
Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis.
To present recent data on discordant tubal blockage (DTB), its influence on pregnancy rates and how women should gage their fertility when screening and diagnostic tests don’t always agree. This retrospective cohort study included 78 infertile women, who underwent tubal patency assessment between January 2016 and June 2024 at the Clinical Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna. Tubal patency was assessed twice. Initial assessment of tubal patency had been performed by hysterosalpingo-contrast sonography (HyCoSy) or hysterosalpingography (HSG) and had suggested bilateral occlusion in the DTB group (n = 38) and bilateral patency in controls (n = 38). Bilateral patency was found in all patients during subsequent laparoscopic chromopertubation. The primary outcome parameter was the clinical pregnancy rate within 6 months. The basic patient characteristics showed no significant differences between the DTB and the control groups. Clinical pregnancy was found in 47.4