Clomiphene Citrate Stimulation Research Articles

Hormonal changes in consecutive clomiphene citrate stimulation cycles and their effect on pregnancy rates.

Objective:To determine the relationship between the cumulative effect of sequential clomiphene citrate (CC) treatments in unexplained infertile women with intercycle and intracycle serum hormone changes.Materials and Methods:Patients who received CC 50 mg in the first cycle (group I, n=34) as ovulation induction and those who received CC 50 mg in the second consecutive cycle (group II, n=18) were compared. Basal (cycle days 2-5) and trigger day (the day that recombinant human chorionic gonadotropin is given) levels of gonadotropin and steroid hormones were measured.Results:The 17OHP increase on trigger day was found to be statistically significantly higher in group II compared to the basal day (p=0.083). The testosterone (T) response on the trigger day of the patients in group II was found to be statistically significantly higher than that in group I (p=0.023). The number of selected follicles was negatively correlated with a follicle-stimulating hormone decrease and positively correlated with an estradiol increase. Endometrial thickness was positively correlated with a luteinizing hormone increase, and cycle cancelation was positively correlated with decreased estradiol.Conclusion:Based on this study, it was concluded that the reason for the increased efficiency rate in successive cycles of CC may be the cumulative increase in T and 17OHP levels. However, this result was found not to affect the clinical pregnancy rate.

P-061 What is the optimal number of IUIH cycles before changing treatment ?

Abstract Study question Is there an optimal number of intrauterine inseminations before offering another treatment for unexplained infertility, taking into account cumulative pregnancy rate and drop out? Summary answer Up to 3-4 intrauterine inseminations are advisable for unexplained and mild male infertility, as this will provide the optimal chances for the patient. What is known already Intrauterine insemination has been used as a first line treatment for unexplained infertility and mild male subfertility. However, during the years great debate and only few randomised controlled studies has been published supporting this. It has been shown that up to 3 inseminations are comparable to an IVF cycle. Further, multiple gestations can be managed and reduced in inseminations as well. Thus, up to 3 cycles of intrauterine inseminations can increase the chances of a healthy offspring and in controlled trials are comparable to an IVF cycle. Study design, size, duration The study is a retrospective cohort study including all patients in treatment for unexplained infertility, anovulation disorders or mild male factor from 2005 to 2022 in a single fertility clinic. Inclusion criteria: more than 1 year of infertility, normal or moderate sperm parameters. A total of 3729 women were included and all followed until pregnancy or drop out. A total of 9459 cycles were included. Participants/materials, setting, methods Women between 18 and 40 years were included. All had more than 1 year of infertility and suffered from unexplained infertility, mild male factor or ovulation disorders. All women received a mild oral tamoxifen or clomiphene stimulation for 5 days and when the leading follicle was 17 mm in diameter an ovulation induction with Fyrmadel 0,25 mg was used. All inseminations after Percoll centrifugation. Pregnancy in 12 weeks were recorded including number of gestations. Main results and the role of chance We found a cumulative pregnancy rate for 3 cycles to be 29%, for 4 cycles 32%, for 5 cycles 35%, for 6 cycles 37%, and a corresponding cumulative drop out of; for 3 cycles; 33%, for 4 cycles;43% for 5 cycles; 50%, for 6 cycles 55%. Multiple gestations were found to be 4%. Using this large data material, we found that 3-4 intrauterine inseminations were acceptable due to the cumulative pregnancy rate and drop numbers. Increasing the number to more cycles did not benefit the patient’s chance significantly and should not be recommended. The study was able to identify all cycles from any individual person starting the treatment and therefore the drop out form a main fertility clinic could be estimated properly. No hyperstimulation’s syndrome were identified and a multiple gestational risk of 4 % were identified. Limitations, reasons for caution A retrospective study from 2005 to 2021 with the limitations that a retrospective carries. The lab procedure/stimulation protocol were the same which makes the results robust. This study involved a large number of patients (3729) every cycle were followed until they got pregnant and dropped out until the 6th cycle. Wider implications of the findings Intrauterine insemination is a safe and efficient treatment option for a group of infertile women. This study describes the relative high drops out after 4-5 cycles and a cumulative pregnancy rate of 30-33% following 3-4 cycles. hereafter the cumulative pregnancy rate does not rise significantly and drop out increases. Trial registration number na

IVF Lite: a smart IVF programme based on mild ovarian stimulation for good prognosis patients

Research questionThe IVF Lite programme is based on mild ovarian stimulation including up to three fresh/frozen embryo transfers within 12 months. Is it effective and safe in good prognosis patients? DesignSingle-centre prospective study on infertile patients at their first IVF attempt (female age ≤38 years, anti-Müllerian hormone concentrations >1.5 ng/ml and/or FSH ≤10 mIU/ml). Induction of multiple follicular growth was based on a fixed protocol consisting of clomiphene citrate (100 mg/day) from day 3 to 7 of the menstrual cycle and 150 IU of recombinant FSH on days 5, 7 and 9. In case of low follicular recruitment (fewer than four follicles), the cycle was cancelled. The IVF Lite programme was considered complete after a live birth delivery or up to three embryo transfers within 12 months. The primary outcome was the cumulative live birth rate (cLBR) per couples that completed the programme. ResultsA total of 369 patients completed the IVF Lite programme, with 239 live births; 132 patients delivered after one embryo transfer (35.8%), 70 after a second embryo transfer (cLBR 54.7%), and 37 after a third attempt (cLBR 64.8%). No cases of ovarian hyperstimulation syndrome or clinical complications occurred. Spontaneous dropout rate from the programme was 4.5%. The cLBR per intention to treat was 46.8%. ConclusionsThe IVF Lite programme proved to be effective and safe in good prognosis patients with a good response to clomiphene citrate stimulation. It was well tolerated and implied low gonadotrophin consumption. Two-thirds of the patients achieved a live birth at the completion of the programme.

Mild Ovarian Stimulation for Infertility in Women with Polycystic Ovary Syndrome

Objective: The aim of this study was to explore the effect of clomiphene citrate (CC) on the cycle characteristics and outcomes of women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation. Methods: This is a cross sectional study, and it was conducted at the tertiary-care medical center. This study included 55 PCOS patients and 54 patients without PCOS undergoing ovarian mild stimulation. In the study group (n = 55), CC and human menopausal gonadotropin (HMG) were administered simultaneously beginning on cycle day 3, while in the control group without PCOS (n = 54) a differing protocol treatment was used. The primary outcome measure was the stimulation day, HMG dose, number of dominant follicles, serum E2, LH, P4 in trigger day and number of oocytes. Secondary outcomes included the number of top-quality embryos, maturation rate, fertilization rate, cleavage rate, incidence of premature LH surge, and OHSS, biochemical and clinical pregnancy rate. Results: The study group received obviously a lower total HMG dose [470.54 ± 304.5 (375–975) vs. 500.00 ± 287.59 IU, but similar HMG duration. While the antral follicle count (AFC) was higher in the study group, the number of oocytes retrieved and top-quality embryos was remarkably less [5 (0 – 30) vs. 13 (0 – 42), 2 (0 –14) vs. 3.5 (0 – 15), p = 0.003, respectively]. The mature oocyte rate was higher in the study group (p = 0.036). No significant differences were detected in fertilization rate and cleavage rate between the 2 groups. CC had a positive influence (higher oocytes retrieved and top-quality embryos) on cycle characteristics, but might be correlated with the impaired IVF outcomes (lower E2, lower implantation rate) in PCOS patients undergoing IVF, when CC + HMG was used simultaneously. Conclusion: In women with PCOS, mild CC stimulation resulted in increased oocytes and viable embryos compared with the control group. The study regimens had a low incidence of OHSS. The results of the CC combined regimen provide new insights into the development of a more patient-friendly protocol for women with PCOS. However, this study needs to be continued on more samples in the future.

Impact of Clomiphene Citrate on the Steroid Profile in Dysmetabolic Men with Low Testosterone Levels.

Clomiphene citrate (CC) in male hypogonadism increases testosterone (T) and estrogen levels by stimulating pituitary gonadotropin release. Our group confirmed these hormonal changes in a randomized, cross-over, double-blind trial of CC versus placebo in addition to metformin, conducted in 21 obese dysmetabolic men with low T levels. However, we hypothesize that based on its mechanism of action, CC may directly or indirectly affect adrenal steroidogenesis. The aim of this sub-study was to better understand the changes in steroid levels and metabolism induced by CC treatment. We assessed 17α-hydroxypregnelone (17αOH-P5), dehydroepiandrosterone (DHEA), progesterone (P4), 17α-hydroxyprogesterone (17αOH-P4), androstenedione (A), T, dihydrotestosterone (DHT), estrone (E1), 17β-estradiol (E2), 11-deoxycortisol (11 S), cortisol (F), and cortisone (E) by LC-MS/MS, and corticosteroid binding globulin (CBG) by ELISA, before and after each treatment. In addition, free-F and steroid product/precursor ratios were calculated. We observed a significant change in serum levels induced by CC compared with placebo for 17αOH-P4, DHT, T, E2, E1, F, E, and CBG, but not free-F. In addition, compared to placebo, CC induced higher 17αOH-P4/P4, E2/E1, 17αOH-P4/17αOH-P5, A/17αOH-P4, T/A, E1/A, F/11 S, and F/E ratios. Therefore, besides the CC stimulating effect on testis steroidogenesis, our study showed increased F, E, but not free-F, levels, indicating changes in steroid metabolism rather than adrenal secretion stimulation. The steroid profiling also revealed the CC stimulation of the Δ5 rather than the Δ4 pathway, thus indicating considerable testicular involvement in the increased androgen secretion.

Basal Anti Mullerian hormone levels and endometrial thickness at midcycle can predict the outcome after clomiphene citrate stimulation in anovulatory women with PCOS, a retrospective study

PurposeRecent studies reported that in polycystic ovary syndrome (PCOS) patients, other stimulation agents are superior to the popular first-line regimen, clomiphene citrate (CC) for ovarian stimulation. Nonetheless, CC is still widely used since it is not clear which patients will not respond to it. Furthermore, the prognostic value of endometrium thickness at midcycle is controversial. We aimed to find factors predicting the response to CC and the prognostic value of endometrial thickness at midcycle.MethodsWe collected data retrospectively from 89 anovulatory PCOS patients who had the first stimulation with 50 mg CC. We analyzed the basal levels of AMH, testosterone, LH, LH:FSH ratio and the endometrial thickness at midcycle by univariate, followed by multivariate regression. The outcome measures were pregnancy, follicle maturation and endometrial thickness at midcycle.ResultsStimulation with 50 mg CC resulted in follicle maturation in 50.6% of the women and in 27.0% pregnancies. In the univariate analysis, greater endometrial thickness, lower LH and AMH levels and a lower LH:FSH ratio were associated with pregnancy (p < 0.05). In the multivariate analysis, only endometrial thickness remained predictive (p = 0.045). The endometrial thickness cutoff level of ≥ 8 mm showed a sensitivity of 87.5% (96% CI 67.6–97.3) and a specificity of 66.7% (95% CI 43.0–85.4) for prediction of pregnancy. In the multivariate analysis AMH levels 5.4 (3.4; 7.0) (ng/mL) predicted pregnancy (β = − 0.194 ± 0.092; p = 0.034)ConclusionWe suggest to refrain from CC as first-line regimen in patients with AMH > 7 ng/ml. Under CC treatment, the cutoff value of ≥ 8 mm endometrium thickness at midcycle is associated with a better outcome.

Changes in serum markers of patients with PCOS during consecutive clomiphene stimulation cycles: a retrospective study

BackgroundA retrospective case-control study was performed to evaluate whether PCOS-specific serum markers would change in women with polycystic ovary syndrome (PCOS) during the course of two consecutive cycles of clomiphene citrate (CC)-stimulation, which did not lead to a pregnancy.MethodsAnovulatory PCOS patients who underwent two consecutive CC-cycles (n = 41) and anovulatory PCOS controls who chose an observational approach for two months (n = 24) were included in the study. The main outcome measures were levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH), total testosterone, androstenedione, and sexual hormone binding globulin (SHBG).ResultsIn the control group, PCOS-specific serum parameters did not change during two months (p > 0.05). In the CC-group, there were decreases in LH (11.8 ± 4.9 mU/mL vs. 10.9 ± 4.0 mU/mL; p = 0.029), the LH:FSH ratio (2.1 ± 0.8 mU/mL vs. 1.8 ± 0.5 mU/mL; p = 0.007), and AMH (8.08 ± 4.27 ng/mL vs. 7.17 ± 3.37 ng/mL; p = 0.011), as well as an increase in SHBG (46.0 ± 20.2 nmol/L vs. 51.2 ± 21.0 nmol/L; p < 0.001). A higher age and lower baseline total testosterone and AMH levels were predictive of an AMH decline (p < 0.05).ConclusionTwo cycles of CC-stimulation that did not lead to a pregnancy were accompanied by mean LH, AMH, and LH:FSH ratio declines and an SHBG increase. The clinical significance seems of minor relevance.

Quintuplet Pregnancy: A Rare Case after Clomiphene Citrate Therapy and Review of Literature

Multiple pregnancies are increasing with the progress in Assisted Reproductive Technology. The authors report a case of quintuplet pregnancy after Clomiphene Citrate stimulation. This is a 28-year-old woman, G2, P1 with a 4-year-old child alive, who consulted for maternity desire. She was treated with Clomiphene Citrate at 100 mg daily for five days. The presence of a quintuplet pregnancy at 8 weeks + 5 days was found by ultrasound on 29/12/2018. During the follow up of the pregnancy, she presented pre-eclampsia from 24th week (TA 140/100 mmHg, significant proteinuria, edema of lower limbs). Methyl Dopa treatment was instituted. Tocolytic treatment with Salbumol was prescribed facing uterine contractions at 30 weeks. The patient had premature rupture of membranes at 34 weeks + 4 days, followed by uterine contractions. She had a cesarean section at the same day with the birth of five newborns alive. This is the first reported case in Burkina Faso.

Evaluation of Controlled Ovarian Hyperstimulation Gonadotropin Stimulation and Clomiphene Citrate Stimulation Cycles in Infertile Women

Evaluation of Controlled Ovarian Hyperstimulation Gonadotropin Stimulation and Clomiphene Citrate Stimulation Cycles in Infertile Women

Effect of oral Tadalafil on endometrial thickness in patients receiving Clomiphene citrate for ovulation induction

Abstract Background Adequate and optimum endometrial development is required for a successful pregnancy to occur. Clomiphene citrate is well known for its negative impact on endometrial thickness. The long-acting phosphodiesterase 5 inhibitor, Tadalafil, was shown to improve endometrial growth in patients under Clomiphene citrate stimulation. Objective To study the effect of Tadalafil on the endometrial thickness in Clomiphene citrate stimulated cycles as compared to clomiphene citrate alone and human menopausal gonadotropins. Study design A randomized controlled study. Setting was at the infertility clinic of Cytogenetic and Endoscopy Unit, Zagazig University Hospital. Material and methods The study included 236 patients who underwent a single cycle of ovulation induction and timed intercourse. Patients were divided into 3 groups: Controlled ovarian stimulation was done in group A by Clomiphene Citrate alone, in group B by Clomiphene Citrate with addition of Tadalafil and in group C by Human Menopausal Gonadotropins. Results As regard the number of cases who got pregnant, we found that there was a statistically significant difference (P Conclusion This study showed that the pregnancy rate achieved with Clomiphene citrate/Tadalafil combination was comparable to that achieved by Human Menopausal Gonadotropins and significantly higher than with Clomiphene citrate alone. This was attributed to the improvement of endometrial thickness by Tadalafil in Clomiphene citrate stimulated patients.

Nitric oxide donors increase the pregnancy rate in patients with unexplained infertility undergoing clomiphene citrate stimulation and intrauterine insemination: a randomized controlled pilot study

This study evaluated the effects of nitric oxide donor’s treatment on the pregnancy rate and uterine blood flow in patients with unexplained infertility undergoing clomiphene citrate stimulation and intrauterine insemination. A total of 120 patients were randomly allocated to a control group who received 100 mg clomiphene citrate daily from day 5 to 9 of cycle plus placebo vaginal tablets, and a study group received clomiphene citrate plus isosorbide mononitrate 10 mg vaginal tablets. Vaginal ultrasound was done before treatment and every other day starting from day 12 of cycle to count mature follicles and ovulation was triggered by IM injection of 10 000 IU hCG when one follicle measured 18 ≥ mm followed by intrauterine insemination after 36 h. The endometrial thickness, uterine arteries resistance and pulsation indices, and endometrial vascular flow and vascular flow indices were measured before treatment and at day of hCG injection. Results were analyzed after one cycle treatment using the Mean ± SD, the Student t test and the Fisher Exact test. Significant result was considered at p values <0.05. The study group had significant higher pregnancy rate/cycle, higher endometrial and lower uterine artery blood flow indices (p < 0.05).

Widening access to infertility care by offering affordable IVF protocols: the Mexican experience

Despite considering procreation a human right, it is a harsh reality that access to assisted reproductive techniques (ART) constitutes a privilege among couples suffering infertility. Among the many barriers the cost and the availability of IVF clinics willing to provide affordable services are the major obstacles for the provision of treatments. In an effort to make ART more accessible our institute begun offering 2 major variants for in vitro fertilization and here are the summary of outcomes. Prospective and descriptive study. The two variants offered were In Vitro Maturation of oocytes (IVM) and clomiphene citrate stimulation for in vitro fertilization (CCS IVF), performed between January 2011 and August 2015. Patients included for either protocol had to have regular menstrual cycles, tubal factor or mild male factor or unexplained infertility. The choice for either IVM or CCS-IVF relied on the affordability of the minimal budget. IVM was performed during a natural cycle and for the CCS-IVF, the doses were between 100 to a max of 150 mg/daily for 5 days. Cycles were considered canceled due to absent oocytes, no fertilization, and no embryo cleavage. Sixty-tree cycles were included for IVM (group 1) and 56 cycles in the CCS IVF (group 2). The mean age was 31.9±3.2 for group 1 and 33.1±4.0 for group 2. In group 1, 18 cycles were canceled (33%). Fertilization rate was 77% and cleavage rate was 62%. Embryos were transferred on day 3 of development. The clinical pregnancy rate was 29% (12/41) and the ongoing/delivered rate was 22%. For group 2, 13 cycles were cancelled (25%). Fertilization and cleavage rate were 76% and 97%, respectively. A total of 11 clinical pregnancies (26%) were documented and 6 ongoing/delivered (19%). Implantation rate was 11% and 13%, respectively. The cost of the entire cycle of IVF with the variant protocols was one third of the conventional treatment. The two modified ART protocols offer acceptable opportunities for pregnancies to patients with limited economical resources, otherwise unable to afford standard IVF treatments. The creation of cost-effective approaches to IVF improves and widens access to care. Fine-tuning protocols may be required to reduce cancellation rates and improve delivery rates.

Subclinical hypothyroidism is associated with metabolic syndrome and clomiphene citrate resistance in women with polycystic ovary syndrome

Background: To evaluate the possible relationship between subclinical hypothyroidism (SCH) and metabolic syndrome (MS) and the response to clomiphene citrate (CC) stimulation in women with polycystic ovary syndrome (PCOS).Methods: One hundred and ninety-six women with PCOS were divided into two groups: (1) the SCH group with 92 patients; (2) the euthyroid (EU) group with 104 patients. Physical characteristics and metabolic parameters as well as the reaction to CC stimulating test were compared between these two groups.Results: (1) In the SCH group, significantly higher body mass index, Ferriman–Gallwey score, serum triglyceride, insulin and glucose of oral glucose tolerance test, homeostatic model assessment-insulin resistance (HOMA-IR) and significantly lower serum high-density lipoprotein cholesterol was observed in comparison with those in the EU group (p < 0.05). (2) The prevalence of CC resistance (30.4%), IR (43.5%) and MS (34.8%) in the SCH group was significantly higher than that in the EU group (p < 0.05).Conclusions: SCH was found associated with IR, MS and CC resistance in women with PCOS. PCOS patients with SCH may have a poorer treatment response to ovulation induction with CC.

Estradiol regulates human QT-interval: acceleration of cardiac repolarization by enhanced KCNH2 membrane trafficking.

Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-α-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein-90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane. Elevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT-2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor-α-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues.

Ovarian reserve markers in unexplained infertility patients treated with clomiphene citrate during intrauterine insemination.

IntroductionThe aim of this retrospective case control study was to identify predictors of ovarian response and pregnancy outcomes in intrauterine insemination (IUI).Material and methodsOne hundred women undergoing IUI cycles with clomiphene citrate were enrolled. The number of antral follicles and the total ovarian volume by ultrasound, and the basal levels of follicle-stimulating hormone (FSH), estradiol, and inhibin B on cycle day 3 were measured in groups that were divided according to ovarian response. The tests were also evaluated according to ovarian response and pregnancy outcomes. All analyses were performed using the Statistical Package for the Social Sciences, version 15.0 (SPSS, Chicago, IL, USA).ResultsThe antral follicle count (AFC) was the best single predictor for ovarian response and pregnancy outcomes. The sensitivity and specificity for prediction of ovarian response were 81% and 78% for AFC at an optimum cutoff value of ≤ 13.1. Age was negatively correlated with ovarian volume (r = –0.280, p = 0.021) and AFC (r = –0.358, p = 0.003). Increasing FSH was associated with a reduction in AFC (r = –0.273, p = 0.025). The AFC was significantly correlated with ovarian volume (r = 0.660, p < 0.0001) and FSH (r = –0.273, p = 0.03).ConclusionsOur data demonstrate that the AFC provides better prognostic information on the occurrence of ovarian response during clomiphene citrate stimulation for IUI.

Dynamics of anti-Müllerian hormone during controlled ovarian stimulation

Aim: To evaluate the dynamics of anti-Müllerian hormone (AMH) during controlled ovarian stimulation (COH) and to correlate changes in AMH to age, estradiol (E2) levels, and the presence of polycystic ovary syndrome (PCOS).Methods: Data were retrospectively collected from women presenting for COH in the outpatient clinic of a university hospital between January and July 2011. Concentrations of AMH and E2 during COH with gonadotropins for in vitro fertilization (IVF) (n = 68) and clomiphene or low-dose gonadotropin stimulation cycles (n = 27) for intrauterine insemination were evaluated. Percentage change in AMH and E2 from pre-stimulation values was calculated. Dynamics of hormonal changes were analyzed using non-parametric tests. Correlations between changes in AMH and E2 were analyzed with Spearman correlation.Results: During IVF stimulation, AMH declined steadily from pre-stimulation values. No significant change in AMH dynamics was observed during clomiphene or low-dose stimulation cycles. Percentage decline in AMH during IVF stimulation correlated with rise in E2 at all time points.Conclusions: The observed phenomena contribute to an improved understanding of AMH expression and its role in the follicular development. Our data support the concept that AMH is produced by secondary, preantral and small antral follicles in the early part of stimulation and declines as these follicles are recruited into dominant growing follicles.

The effect of ovarian stimulation on the outcome of intrauterine insemination

Although intrauterine insemination is one of the oldest techniques in reproductive medicine, its significance is still controversially discussed. Many factors have been reported as influencing pregnancy rates after IUI. The aim of this retrospective analysis is to evaluate the success rate of repeated inseminations depending on the type of ovarian stimulation. Patients who underwent intrauterine insemination in Wiesbaden Kinderwunschzentrum between 1998 and 2010, not older than 45 years of age, with male subfertility were included in this study. On the whole, 5,346 inseminations on 2,180 patients were analyzed retrospectively. Females' mean age was 34.1, ranging from 19-45 years. In 433 cycles an insemination was performed during a natural cycle. 4,020 cycles were stimulated with recombinant FSH, 596 cycles with clomiphene, 194 with urinary FSH, 103 with HMG. The pregnancy rates range from 7.4% in the clomiphene group to 14.4% in the urinary FSH group. Clomiphene stimulation seems to offer the significantly lowest pregnancy rate (p = 0.03). The other types of stimulation do not differ significantly from each other concerning the pregnancy rate. Patients under 39 years of age do not profit from any ovarian stimulation. In 40 and more years of old patients, pregnancy rates are higher, if any stimulation was performed. To sum up, clomiphene stimulation showed to offer significantly lower pregnancy rates in comparison to the natural cycle, FSH stimulation and HMG stimulation in IUI treatment. While women younger than 40 seem not to profit from any ovarian stimulation, women over 40 do profit.

A randomized controlled trial of fallopian tube sperm perfusion compared with standard intrauterine insemination for women with non-tubal infertility

Does fallopian tube sperm perfusion (FSP) result in better pregnancy and live birth rates than standard intrauterine insemination (SIUI) for couples with non-tubal infertility with or without gonadotrophin or clomiphene stimulation? There was no evidence of an improvement in live birth rates with FSP compared with SIUI. Previous randomized controlled trials have suggested improved live birth rates with FSP but these trials were small. A systematic review published in 2004 suggested heterogeneity in results. This pragmatic, multicentre, randomized controlled trial compared SIUI and FSP in 417 women with non-tubal infertility. The patients were treated at fertility clinics in New Zealand, Australia and the United Arab Emirates. Four hundred and seventeen women were randomized to SIUI (n = 210) or FSP (n = 207). Data were available for analysis from 198 women in the SIUI group and 198 women in the FSP group. There were 19 women with incomplete data because of cycle cancellation or withdrawals and 2 women who conceived prior to commencing treatment. There were no significant differences in live birth rates between the two groups with 27 (12.9%) in the SIUI group and 21 in the FSP group (10.1%) [Odds Ratio (OR) 1.31 (0.71, 2.39), P = 0.48]. Two ectopic pregnancies were reported in the SIUI group and one was reported in the FSP group. Different ovulation protocols were used in the different clinics. Approximately 10% of the cycles involved donor sperm and ∼5% of the cycles did not complete the assigned intervention. There was no evidence of an improvement in live birth rates with FSP compared with SIUI. The study was funded in part by the A+ trust of the Auckland District Health Board. No commercial funding was received. ANZCTR Number ACTRN12612001303831.

Clomiphene Stimulation Test in Men Abusing Anabolic-Androgenic Steroids for Long Time

Objective: Androgenic-anabolic steroids (AAS) are commonly used by athletes and recreational athletes. In some cases they induce persistent anabolic steroid-induced hypogonadism (ASIH). Design: In an observational study we assessed the function of the pituitary-gonadal axis in a series of men with suspected ASIH. Methods: Clomiphene stimulation test (CST) was performed in 13 hypogonadal adult men with previous, prolonged exposure to AAS. We evaluated the response of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and total testosterone (T) to 50 mg of clomiphene daily administered for a week. Results: Mean concentrations of hormones before and after clomiphene administration were respectively (mean ± SD): 3 ± 1.2 and 8.3 ± 2 mIU/ml for LH; 3 ± 1.1 and 10 ± 14.6 mIU/ml for FSH; and 2.3 ± 0.6 and 7.2 ± 1.7 ng/ml for T (p<0.001). Conclusions: Men with ASIH, after a long-time withdrawal of AAS, present an intact reaction of gonadotropins and testosterone to clomiphene stimulation.

Parameters for calcium metabolism in women with polycystic ovary syndrome who undergo clomiphene citrate stimulation: a prospective cohort study

To evaluate whether parameters for calcium metabolism were associated with characteristics of polycystic ovary syndrome (PCOS). A prospective cohort study. Ninety-one anovulatory, infertile women with PCOS patients underwent clomiphene citrate (CC) stimulation. Main outcome measures were parathyroid hormone (PTH); 25-hydroxyvitamin D3 (25OHD3); serum levels of calcium, phosphorus, magnesium, albumin, and total protein; the serum calcium-phosphorus product; LH; FSH; sexual hormone binding globulin; testosterone; and androstenedione. PTH correlated inversely with serum calcium (r=-0.235; P=0.004) and 25OHD3 (r=-0.664; P<0.001), whereas positive correlations were found between PTH and body mass index (BMI; r=0.270; P=0.010) and between PTH and testosterone (r=0.347; P=0.001). After stimulation with 50 mg CC, 57.1% (52/91) developed a follicle, whereas 26.4% (24/91) became pregnant. In a multivariate model to predict both follicle development and pregnancy, BMI and 25OHD3 deficiency were significant predictive parameters. 25OHD3 deficiency was an independent predictive parameter of CC stimulation outcome, in terms of follicle development and pregnancy. Our results suggest a substantial role of vitamin D in PCOS and infertility treatment in these patients.