Administration Of Clomiphene Citrate Research Articles

TREATMENT OUTCOMES IN PCOS (POLYCYSTIC OVARIAN SYNDROME)-RELATED INFERTILITY

Polycystic ovarian syndrome (PCOS) is one of the underdiagnosed endocrine disorders found to be prevalent among females in the reproductive age group. PCOS effects on an average 8-13% of reproductive aged women, globally. This condition is responsible for causing distress physiologically and psychologically paving the way for a poor quality of life. One of the devastating complications of PCOS is infertility. At present, there is no treatment for PCOS but could be managed by alternate options such as lifestyle modification to in-vitro fertilization. The primary objective of this review article is to analyze the outcomes of certain pharmacological treatment options such as clomiphene citrate which is a selective estrogen receptor modulator, Letrozole an aromatase inhibitor, and gonadotropins for PCOS-related infertility. Clomiphene citrate binds to estrogen receptors indirectly increasing the gonadotropins. Studies confirm a 35-40% successful outcome. Letrozole similarly increases gonadotropins by indirectly decreasing estrogen. A notable increase in the successful outcome was observed with both clomiphene citrate and letrozole, with almost near similar results. The pregnancy outcome was approximately 40% with clomiphene citrate, while letrozole showed 50%. Notably, more side effects were observed in the administration of clomiphene citrate compared to letrozole. Human menopausal gonadotropin (hMG) and recombinant follicle-stimulating hormone (FSHr), that are gonadotropins, were used as they are directly responsible for the maturation of follicles and ovulation itself. The use of gonadotropins increased the pregnancy rate outcome to 20 -30 %, albeit with the risk of multiple births. Furthermore, we have discussed why letrozole and clomiphene citrate are used as the primary therapy compared to gonadotropins. Peer Review History: Received 22 May 2024; Reviewed 14 July 2024; Accepted 23 August; Available online 15 September 2024 Academic Editor: Dr. Rola Jadallah, Arab American University, Palestine, rola@aauj.edu Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. George Zhu, Tehran University of Medical Sciences, Tehran, Iran, sansan4240732@163.com Dr. Ogbonna B. Onyebuchi, Nnamdi Azikiwe University, Awka, Nigeria, summitpharm@yahoo.com

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

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

Evaluation of Ovarian Histomorphology and Function Following Clomiphene Citrate and Human Chorionic Gonadotropin Administration in Wistar Rats

Polycystic ovarian syndrome (PCOS), affecting 5-10% of women, is a leading cause of infertility affecting 10-15% of couples globally. Human chorionic gonadotropin (hCG) and clomiphene citrate (CC) are often utilized for the treatment of PCOS. Accordingly, this study explored the effects of CC and hCG on ovarian histomorphology and fertility parameters. Twenty adult female rats were divided into four groups as follows: Group A (control) received only feed and water; Group B received 0.7 mg/kg BW of CC twice daily for five days and was mated before sacrifice on day 19 (before litter); Group C received 0.7 mg/kg BW of CC twice daily for five days, followed by mating and allowed to litter before sacrifice; Group D received 0.7 mg/kg body weight (BW) of hCG on day one, followed by 0.7 mg/kg BW of CC twice daily for five days, and were mated before sacrifice on day 7 (before litter). Results showed that Group B rats had higher, more than other groups, Follicle-stimulating hormone (FSH), Estradiol, Testosterone and Prolactin levels when compared to the control. Similarly, rats in Group B had higher levels of Progesterone while Group D had higher levels of Luteinizing hormone (LH) when compared to the control group. Histological findings demonstrated diverse impacts on ovarian structures, ranging from congested blood vessels to haemorrhages and follicular cysts. Consequently, this study underscores the complexities of drug interactions in reproductive health and provides preliminary insights into the possible adverse effects of CC and hCG on the ovary and fertility parameters.

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

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. 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. PCOS. Cheek acupuncture therapy. Both of them successfully conceived and gave birth to a liveborn baby. 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.

Usefulness of Newly Devised Clomiphene Citrate Administration Method Compared with the Conventional Method in Ovulation and Pregnancy

Usefulness of Newly Devised Clomiphene Citrate Administration Method Compared with the Conventional Method in Ovulation and Pregnancy

Effect of Aqueous Leaves Extract of Datura alba ness (Thorn Apple) on Gonadotropic Hormones (FSH, LH) and Prolactin Following Administration of MSG and Clomiphene Citrate in Female Wistar Rats

Phytomedicine has become popular among and majority of women depends on herbal medicine when seeking healthcare. Several women opted for herbal medicine when looking for fertility and most the women that hormonal imbalance depends on herbal medicine for correction. Hormones is substance that must be required and must be in the right values for reproduction to occur. The aim is this study is to ascertain the Effect of aqueous leave extract of D. alba ness (Thorn Apple) on gonadotropic hormones (FSH, LH) Treated with monosodium glutamate (MSG) and clomiphene citrate in female wistar rats. The animals were randomly selected into 7 with five animals per group. Each group received the following: group 1 10mls/kg of distil water, group 2 low dose of extract (1000mg/kg), group 3 high dose of extract(2000mg/kg), group 4 MSG 800mg/kg, group 5 clomid 50mg/kg, group 6 MSG + high dose of extract and group 7 clomid+ high dose of extract. Administration of extract was done for 21 days, and on the 22nd day, the animals were sacrificed and blood samples were collected for hormonal analysis. The results revealed significant decreased in the serum levels of follicle stimulating hormones (FSH) in all the treatment groups (extract 1000mg/kg, extract 2000mg/kg, MSG 800mg/kg, MSG 800mg/kg + extract 2000mg/kg, and clomid 50mg/kg + extract 2000mg/kg) when compared with control and significant increase in serum levels FSH in clomid 50mg/kg treated group. Luteinizing hormone (LH) serum levels significantly decreased in all the treatment groups when compared with the control group. LH levels in the clomid group significantly increased when compared with other treatment groups. The statistical analysis was carried out using Statistical Package for Social Science (SPSS) version 23.

Identification and synthesis of (Z)-3'-hydroxy clomiphene as a new potential doping-relevant metabolite of clomiphene.

(E/Z)-3'-HC and (E/Z)-4'-HC were synthesized involving the McMurry reaction. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and optimized after a derivatization step with dansyl chloride to separate eight HC isomers. Using this method, urine samples from a controlled clomiphene administration study were analyzed, in which male study participants received therapeutic doses of clomiphene for 30 days and collected urine samples for up to 8months. Thus, isomer-specific HC elimination profiles could be monitored. The metabolite previously found in doping-control samples was identified as (Z)-3'-HC. The elimination profiles of the different HCs confirmed previous results, with (Z)-3-HC being the most abundant urinary hydroxy metabolite shortly after administration. A new finding was that the data suggest that (Z)-3'-HC is excreted at higher relative concentrations only several weeks after drug intake. These findings might be of particular importance in sport drug testing as they can assist in the decision-making process to distinguish between intentional doping and inadvertent exposure to clomiphene via food contamination.

P-633 Progesterone elevation on the day of trigger in the presence of low ovarian response signifies abnormal follicular environment and poorer oocyte health

Abstract Study question Is progesterone elevation (PE) in the presence of low number of follicles (unexpected PE) associated with oocyte or embryo quality? Summary answer PE on day of trigger in cycles with ≤4 follicles is associated with significantly reduced fertilisation rates and fewer top-quality blastocysts What is known already The negative effect of PE on pregnancy rates in fresh IVF cycles has been demonstrated by multiple studies and meta-analyses, and most studies support no negative effect on oocyte and embryo quality. However, as it is thought that PE is the product of cumulative secretion of low levels of progesterone from multiple developing follicles, PE in the presence of a low number of follicles (unexpected PE) is considered a different pathophysiological entity. It has been hypothesized, but never proven, that in these cases, PE is the result of follicular dysregulation and that it might indicate poorer follicular and oocyte health. Study design, size, duration This is a multi-centre retrospective analysis of a large cohort (n = 1,393) of IVF/ICSI cycles with a low response to ovarian stimulation (1-4 follicles ≥14mm) performed from January 2018 to April 2022. Only cycles of ovarian stimulation using gonadotrophins and GnRH analogues with a measurement of serum progesterone on the day of triggering final oocyte maturation were included. Natural cycles and cycles involving the administration of clomiphene were excluded. Participants/materials, setting, methods Unexpected PE was defined as serum progesterone levels greater than 4.77 nmol/L (1.5 ng/mL) on day of trigger. The primary outcome was the number of usable blastocysts. Secondary outcomes included the number of oocytes retrieved, two pronuclei (2PN) oocytes, number of top-quality embryos, fertilisation rate and blastocyst formation rate. Generalised estimating equations were used to account for the clustered nature of data. Multivariable regression analysis was performed to control for the effect of multiple confounders. Main results and the role of chance In the univariate regression analysis, the number of oocytes retrieved was not significantly different between cycles with and without PE (mean 2.3 vs. 2.1 respectively; p = 0.550). The number of 2PN oocytes was significantly (p = 0.021) lower in the PE group (mean 0.72, 95%CI 0.31-1.14) compared to the non-PE group (mean 1.21, 95%CI 1.12-1.31). The number of top-quality blastocysts was also significantly (p = 0.003) lower in the PE group (mean 0.03, 95%CI -0.03-0.10) compared to the non-PE group (mean 0.14, 95%CI 0.11-0.17). Fertilisation rates per oocyte retrieved, fertilisation rates per oocyte inseminated and the top-quality blastocyst rate per oocyte retrieved were consistently lower in the PE group at 33.3% (95% CI 19.0-47.6), 26.9% (95% CI 14.8-39.0) and 0.7% (95% CI -0.8-2.1) compared to 58.7% (95% CI 55.8-61.7), 52.3% (95% CI 49.3-55.2) and 5.5% (95% CI 4.3-6.8) in the non-PE group. The negative association of PE with the primary outcome measure of this study was confirmed in the multivariable regression analysis where the number of usable blastocysts was significantly lower in the PE group (adjusted mean 0.14, 95%CI 0.03-0.25) compared to the non-PE group (adjusted mean 0.27, 95%CI 0.23-0.31) after adjusting for confounders. Limitations, reasons for caution This is a retrospective observational study, thus not all confounders may be accounted for. Despite being one of the largest studies conducted in poor responders, the sample size of unexpected PE cycles is relatively small due to its rarity. Therefore, this study may be underpowered to detect smaller effect sizes. Wider implications of the findings This study demonstrates for the first time that unexpected PE on the day of trigger (i.e. in cycles with low ovarian response) is associated with poorer oocyte health as reflected in the reduced fertilisation rates and fewer blastocysts available for transfer. This information can aid in better understanding this phenomenon. Trial registration number Not applicable

In vitro derived embryos produced from mares treated with intravenous clomiphene citrate

Optimizing the number of follicles available for ovum pick-up and in vitro embryo production (OPU-IVP) would increase the efficiency of OPU-IVP sessions. In other species, clomiphene citrate (CC) has been credited with enhancing follicular recruitment through augmented GnRH pulsatility. Our goal was to describe the number of follicles, reproductive hormone secretion patterns, and oocyte developmental potential in mares treated with CC and subjected to OPU-IVP. Six light-breed mares underwent follicle ablation (Day 0) to induce a new follicular wave, followed by administration of 250mcg of cloprostenol (PGF2-α) on Day 6. On Days 10-14, a five-day protocol of 0.5% intravenous CC (Annaji.et.al. AAPS PharmSciTech. 2023; 24:48) was administered at a rate of 2grams/mare/once daily; all mares subsequently underwent OPU on Day 17. Collected oocytes were shipped counter-to-counter to a laboratory for fertilization via intracytoplasmic sperm injection (ICSI). Ovarian follicle counts were performed via transrectal ultrasonography immediately prior to each daily administration of CC (Days 10-14) and on the day of OPU (Day 17); the total number of follicles, in addition to the diameter of the largest follicle (mm) were recorded. Serum samples were collected to quantify and characterize systemic reproductive hormone patterns (i.e., LH, FSH, AMH, and P4); sample collection started on the day of ablation (Day 0) and concluded one week following OPU (Day 24).CORR and PRINQUAL procedures of SAS version 9.4 (SAS Institute, Cary, North Carolina) were utilized to evaluate correlation amongst hormones. The development rate of embryos originating from CC treated mares were compared to development rates of commercial embryos produced during the same time period at the ICSI laboratory. Parametric (T-test) and nonparametric (NPAR1WAY) procedures (SAS) were utilized to compare embryo development rates. For all statistical analyses, significance level was set at p≤0.05. Upon completion of CC treatment, the mean (+/- SEM) diameter of the largest follicle and the mean (+/- SEM) total number of follicles was 40 mm (+/- 5.1 mm) and 11.3 (+/- 1.2), respectively. Significant negative correlations were found between LH and FSH (p=0.007), FSH and the largest follicle (p<0.001), and FSH and total follicle number (p=0.01). Conversely, significant positive correlations were found between LH and the largest follicle (p=0.003), AMH and total follicle number (p=0.01), and AMH and P4 (p=0.008). The overall embryo development rate was 50% for CC treated mares (15/30 injected oocytes) and 36.8% (14/38 injected oocytes) for commercial embryos (p=0.56). Although experimental control mares were not utilized in this pilot study, our results warrant continued investigation to identify the impact(s) of intravenous CC administration on follicular dynamics, OPU-IVP and foal production.

Effect of anti-estrogen and anti-progesterone on spermatogenesis, testosterone production and expression of steroidogenic enzyme genes in adult male rats.

The present study was planned to investigate the anti-spermatogenic and anti-steroidogenic effects of Clomiphene Citrate (CC) an anti-estrogen and Mifepristone (MT) an anti-progesterone in the testis of male rats. Following the oral administration of 1.0mg and 5.0mg/kg b.w/day of each for the duration of 30 and 60 days, quantitation of spermatogenesis, RIA for serum and intra-testicular testosterone levels, western blotting and RT-PCR for expression of StAR, 3β-HSD and P450arom enzymes in the testis was done. Clomiphene Citrate at 5.0mg/kg b.w/day for 60 days significantly reduced testosterone (T) levels however the effect was not significant with the lower doses. Reproductive parameters in animals treated by Mifepristone remained mostly unaffected, however, a significant decline in testosterone levels and altered expression of selected genes was observed in 5.0mg for the 30d treatment group. Clomiphene Citrate at higher doses affected the weights of the testis and secondary sex organs. Seminiferous tubules revealed hypo-spermatogenesis with a significant decrease in the number of maturing germ cells and a reduction in tubular diameter. Attenuation in serum testosterone was associated with the downregulation of expression in StAR, 3β-HSD, and P450arom mRNA and protein levels in the testis even after 30 d of CC administration. The results indicate that the anti-estrogen (Clomiphene Citrate) but not anti-progesterone (Mifepristone) induces hypo-spermatogenesis in rats which are associated with a downregulation of expression of two of the steroidogenic enzymes, 3β-HSD and P450arom mRNA and StAR protein.

Recent clomiphene citrate exposure does not impact subsequent clinical outcomes in single euploid frozen embryo transfer cycles

Do infertile couples who recently utilized clomiphene citrate (CC) for ovulation induction or ovarian stimulation (<90 days previously) followed by a single euploid embryo transfer (SEET) have lower implantation potential compared with patients who were not exposed to CC within 90 days before embryo transfer (ET)? There does not appear to be an association between recent CC exposure and lower implantation potential in patients who undergo a frozen embryo transfer (FET) of euploid embryos. Clomiphene has been found to be associated with lower pregnancy rates when compared against other ovarian stimulation medications. The majority of published research about the effects of CC on implantation potential suggest an anti-estrogenic effect on the endometrium. Quality evidence and information about utilization of CC and its effect on implantation potential after euploid ETs is lacking in the literature. A retrospective cohort study with propensity score matching was carried out. We included all patients that underwent an autologous SEET from September 2016 to September 2022 at a single academic-private ART center. The study group included patients that had utilized CC during either ovulation induction cycles and/or controlled ovarian stimulation at least 90 days before FET. A propensity score-matched control group of patients that were unexposed to CC within 90 days prior to SEET was used for comparisons. The primary outcome was positive pregnancy test (defined as a positive serum β-hCG measured 9 days after ET), with other outcomes including clinical pregnancy, ongoing pregnancy, biochemical pregnancy loss, and clinical pregnancy loss rates per SEET. Multivariate regression analyses fitted with generalized estimating equations were utilized to analyze if there was an association between CC utilization and IVF outcomes. Furthermore, the study evaluated the cumulative effect of CC and endometrial receptivity in vivo and subsequent IVF outcomes. A total of 593 patients with utilization of CC in <90 days before ET were compared with 1779 matched controls. Positive pregnancy test rates were comparable among the control group and the CC exposed groups, respectively (74.3% versus 75.7%, P = 0.79), as were clinical pregnancy (64.0% versus 65.0%, P = 0.60), ongoing pregnancy (51.8% versus 53.2%, P = 0.74), biochemical pregnancy loss (15.7% versus 14.03%, P = 0.45), and clinical pregnancy loss rates were also comparable among cohorts (17.1% versus 18.1%, P = 0.71). No association was found between utilization of clomiphene and lower implantation rates (adjusted odds ratio 0.95, 95% CI 0.76-1.18). Also, no differences were observed in sub-analyses based on multiple CC utilization periods. Finally, no association was found between the number of consecutive cumulative clomiphene cycles and sub-optimal IVF outcomes. The study has inherent bias that originated from its retrospective design. Serum levels of CC were not measured and sample size for the sub-analyses was small. There does not appear to be an association between recent CC exposure and lower implantation potential in patients who undergo a FET of euploid embryos. This finding remains consistent, even in patients who undergo multiple, consecutive clomiphene cycles prior to ET. There were no long-term effects of CC on endometrial development and clinical characteristics examined in this study. Patients that utilized CC medication prior to a SEET cycle for either ovarian stimulation or ovulation induction, can be assured that there is no evidence of a residual effect of recent CC administration that could jeopardize their pregnancy probability. No funding was received for the realization of this study. A.C. is advisor and/or board member of Sema4 (stakeholder in data) and Progyny. The other authors have no conflicts of interest to declare. N/A.

Observational study of changes in dominant ovarian follicle with and without administration of clomiphene citrate in primary infertility cases among eastern Indian women

Background: Changing environment and social factors with advancement of science bestowed the human population with both curse and boon. Increasing number of primary infertility is one of the many challenges which is encountered among 3.59% of Indian women population in reproductive age group. Use of clomiphene citrate (CC) is one of the commonly practiced way to find out a ray of hope. Aims and Objectives: The aim of the study was to measure the changes of morphometric parameters of dominant ovarian follicles and their numbers and compare the same before and after administration of CC was the aim of the present study. Materials and Methods: This interventional and cohort study performed on 50 women coming to the infertility clinic at Institute of Post Graduate Medical Education and Research, Kolkata, with primary infertility of reproductive age group. Informed consent was taken from all. Transvaginal ultrasonography was utilized to measure the parameters related with dominant follicles. Comparison among them with respect to number, size, and time to rupture both before and after ovulation induction with CC was made. Results: Statistically significant increase in number and average size of dominant follicle is seen from 1.08 to 2 and 12.26 to 15.31 mm following CC in the third cycle. In polycystic ovarian disease, cases also ovulation has increased significantly. Conclusion: Transvaginal ultrasonography proves to be regarded as a gold standard procedure to measure and monitor the ovarian follicle status. Undoubtedly CC can be regarded as an easy and dependable solution toward treatment of primary infertility.

Various interventions for infertility in men with type II diabetes and hypogonadism

Background: Low levels of testosterone and sexual desire loss are common characteristics of hypogonadism, which is an endocrine disorder often occurring in men. Sexual dysfunction is an uncomfortable condition that both hypogonadal and diabetic men experience nowadays, however the diagnosis and treatment strategies are limited. Type II diabetes is a lifelong disorder of abnormal glucose metabolism with devastating health effects on patients. Sex-related hormones, that normally regulate the reproductive cycle, are found significantly reduced in conditions where the functional activity of the gonads is decreased. An imbalance in the levels of these hormones is also associated with metabolic abnormalities, such as hyperglycemia and insulin resistance. The effectiveness of the existing therapies for sexual dysfunction treatment and the restoration of reproductive hormones in hypogonadal men with type II diabetes remain unexplored. Methods: We searched the Cochrane Library, Scopus, Science Direct and the Web Search engine “Google Scholar” from January 2011 to July 2021. Randomized controlled trials (RCTs) were included, comparing the treatment of sexual dysfunction and the restoration of sex-related hormones in hypogonadal men with type II diabetes with testosterone replacement or administration of vardenafil or clomiphene citrate, versus placebo treatment. Fixed effect meta-analysis was performed to estimate pooled proportions with 95% confidence intervals (CI). Results: The review includes nine RCTs regarding: a) Testosterone replacement therapy (five RCTs) and administration of b) Vardenafil (one RCT) or c) Clomiphene citrate (three RCTs) for the treatment of sexual dysfunction in diabetic men with hypogonadism. The aspects of sexual function were evaluated by estimating the: a) Aging male’s symptoms’ (AMS) rating scale, b) Erectile Function, c) Intercourse Satisfaction, d) Orgasmic Function, e) Sexual Desire, f) Overall Sexual Satisfaction, g) levels of E2 (pg/mL), h) levels of FHS (mU/mL), i) levels of LH (mU/mL), j) levels of SHBG (nmol/L) and k) levels of free testosterone (nmol/L). Our findings suggest that a) testosterone replacement therapy or administration of vardenafil resulted in improved erectile function (95% Cl -0.485 to -0.165; 6 RCTs; I2=94,8%, p=6.5e-05), b) testosterone supplementation ameliorated intercourse satisfaction (95% Cl -0.4 to -0.064; 4 RCTs; I2=54,5%, p=0.006783), orgasmic function (95% Cl -0.674 to -0.325; 4 RCTs; I2=94,6%, p=0) and sexual desire (95% Cl -0.446 to -0.124; 5 RCTs; I2=94,3%, p=0.00509), but had no impact on AMS rating scale (95% Cl -0.286 to 0.057; 4 RCTs; I2=93,1%, p = 0.191643) and overall satisfaction (95% Cl 0.03 to 0.402; 3 RCTs; I2=95%, p=0.023112) and c) administration of clomiphene citrate led in elevated levels of E2 (95% Cl -1.531 to -0.756; 3 RCTs; I2=0%, p=0), LH (95% Cl -0.674 to -0.325; 3 RCTs; I2=0%, p=0), FSH (95% Cl -1.372 to -0.612; 3 RCTs; I2=0%, p=0), SHBG (95% Cl -0.938 to -0.207; 3 RCTs; I2=0%, p=0.002151) and free testosterone (95% Cl -1.864 to -1.204; 3 RCTs; I2=83.1%, p=0), compared to placebo treatment in hypogonadal men with type II diabetes. Conclusions: Hypogonadal males with type II diabetes receiving either testosterone supplementation, or the compounds vardenafil and clomiphene citrate, displayed improved sexual function and elevated levels of sex-related hormones, versus placebo treatment.

Does Clomiphene citrate administration increase success rate of micro TESE in non-obstructive azoospermic men? A randomized controlled trial

Does Clomiphene citrate administration increase success rate of micro TESE in non-obstructive azoospermic men? A randomized controlled trial

Prenatal Restraint Stress-Induced Maternal Exposure and Clomifene Citrate Administration Modulates Reproductive Programming in Female Wistar Rats.

&lt;b&gt;Background and Objective:&lt;/b&gt; Infertility and maternal stress studies have become major public health problems in most societies and this has attracted urgent global attention. This study examined the modulatory role of restraint-induced stress and clomiphene citrate (CC) administration on the reproductive programming of Wistar rats. &lt;b&gt;Materials and Methods:&lt;/b&gt; A total of 119 healthy Wistar rats weighing between 150-200 g were used and assigned into four major groups. Stress was induced for 1, 2, 4 and 6 hrs daily by exposure of the rats to a restraint plastic chamber for 1 and 2 weeks, respectively. At the end of each experimental protocol, the animals were euthanized by cervical dislocation and serum samples were collected for hormonal assay. The average gestational length, litter size and pup weight were examined. Data were expressed as Mean±SEM and mean differences were analyzed using One-way (ANOVA) and LSD &lt;i&gt;post hoc&lt;/i&gt; Test with SPSS 23 at p<0.05 level of significance. &lt;b&gt;Results:&lt;/b&gt; These findings showed that restraint stress caused a significant elevation in corticosterone level, while estrogen, progesterone, follicle-stimulating hormone and luteinizing hormone were significantly reduced when compared with control. Gestation length and litter size were also significantly reduced by stress while pup weights were not significantly affected. The CC increased litter size in unstressed rats when compared to litters of stressed rats that were significantly reduced, although, CC was able to increase the litter size of stressed rats towards normal. &lt;b&gt;Conclusion:&lt;/b&gt; Evidence indicated that stress alters reproductive potential in female rats and also, reduces the effectiveness of CC in inducing ovulation.

P-593 Low dose clomiphene citrate does not reduce implantation rates - a cohort study based on modified Natural Cycle IVF

Abstract Study question Does low dose clomiphene citrate (CC) reduce implantation and eventually pregnancy and live birth rates? Summary answer Low dose CC does not reduce implantation rate and pregnancy and live birth rates – based on the model of modified Natural Cycle IVF (NC-IVF). What is known already CC is commonly used for ovulation induction in the treatment of anovulation or idiopathic infertility. It is also added to NC-IVF cycles to mildly stimulate follicular growth and to inhibit LH surge. CC reduces endometrial thickness and affects endometrial function. Therefore it is assumed that CC negatively affects implantation and thereby reduced pregnancy and live birth per embryo. However, previous studies have shown inconsistent results as previous studies mainly calculated pregnancy rates per cycle but not implantation rate per embryo. Study design, size, duration This cohort study included embryos transferred in NC–IVF and CC-NC-IVF cycles. Women with a maximum age of 42 years were treated at a university hospital between 2011 and 2016. Clinical pregnancy rate and live birth rate per embryo transferred and miscarriage rate per amniotic sac were calculated. Participants/materials, setting, methods A daily dose of 25mg of CC starting on day 5-7 of the cycle until the day of ovulation trigger was applied. A modified mixed effect Poisson regression model was used to account for the number of cycles in the same women and the number of embryos in the same cycle to achieve rate ratios (RR). Adjustment for maternal age, parity, type of infertility, duration of subfertility and indication for IVF were made. Main results and the role of chance 499 couples underwent a total of 1043 IVF cycles, 453 NC-IVF and 590 CC-NC-IVF cycles. Baseline characteristics of both groups were not different. The additional administration of CC did neither decrease clinical pregnancy rate (aRR 1.16; 95% CI: 0.90 – 1.50)[MV1] nor live birth rate per transferred embryo (aRR 1.20; 95% CI: 0.89 – 1.62). Miscarriage rate was also not different in CC-NC-IVF compared to NC-IVF (aRR 1.05; 95%: CI 0.63 – 1.76). Limitations, reasons for caution This study does not allow to draw any conclusions regarding the effect of higher CC dosages. As randomization was not performed, some bias regarding the choice of IVF treatment cannot be completely excluded. Wider implications of the findings As this study revealed for the first time that low dose CC does not affect implantation, low does CC can be used for many different treatments. However, further studies are required to evaluate if this also applies to higher CC dosages. Trial registration number not applicable

Timed Intercourse versus Intrauterine Insemination with Mild Ovarian Stimulation for Unexplained Infertility

Background: Infertility is unexplained in about 22% - 28% of infertile couples. Spontaneous pregnancy may occur in them. If did not happen, Expectant management will be via clomiphene citrate (CC) administration, intrauterine insemination (IUI), and IVF & ICSI. Aim: to assess the effectiveness of intrauterine insemination with mild controlled ovarian stimulation compared with expectant management in couples with unexplained infertility more than one year. Methods: 160 couples with unexplained infertility were selected, The couples were randomly divided into two groups: Group (A) “80 couples”: Intrauterine insemination (IUI) with mild controlled ovarian stimulation (combination of CC + hMG) using prepared semen and was performed 36 hours after hCG injection, Group (B) “80 couples”: Couples had no ovulation induction. They encouraged for timed intercourse in the most fertile days of female cycle guided by folliculometry for 6 months. Data were collected quantitatively, coded and analyzed using SPSS. The power of study is 80% and 95% confidence interval. Result: The pregnancy rate was calculated in both groups: In group (A) (IUI/COS): OPR (Ongoing pregnancy rates) was 27.5% and PR (pregnancy rates)/cycle was 8.6%. In group (B) (Expectant management): OPR was 25% and PR/cycle was 5.3%. Conclusion: Mild controlled ovarian stimulation CC + hMG with IUI offers no statistical significance in terms of pregnancy outcomes over expectant management in this study however significance in the response to stimulation.

Severe Hyponatremia With Partial Hypoadrenalism in Acute Porphyria

Background: Hyponatremia is the most common electrolyte-abnormality in hospitalized-patients, it increases likelihood of hospital death up-to 50% when serum Na<120mEq/L. Syndrome of inappropriate ADH secretion (SIADH) is the most common cause of hyponatremia in hospital inpatients. Clinical Case: 29 years-old woman, hospitalized several times due to severe hyponatremia of 103mEq/L; Admissions were accompanied by severe abdominal-pain and vomiting. She complained of severe premenstrual syndrome with severe abdominal pain and was hospitalized twice after intrauterine insemination. She was euvolemic and due to high urinary-sodium was diagnosed with SIADH. Brain MRI, chest x-ray, thyroid-function test, and 1-mcg ACTH-test were normal. Insulin Tolerance Test for hypoadrenalism was abnormal with cortisol levels of 14.2mcg/dl and 40mg/dl glucose. She was instructed to take strong analgesics and prednisone during attacks, this did not prevent hyponatremia. Finally, due to recurrent abdominal pain, porphyria workup was done and was positive. There are 30 case-reports of porphyria and SIADH. Porphyrias are a group of 8 inherited metabolic-disorders of heme biosynthesis, often classified as hepatic or erythropoietic according to the organ in which heme precursors accumulate. Acute intermitted porphyria is estimated in ~1/75000 people of European descend, yet clinical disease is seen in ~10% of carriers. Attacks present with severe abdominal-pain, nausea, vomiting, constipation, occasionally excretion of red colored urine and signs of increased sympathetic activity. Hyponatremia due to SIADH develops in 40% of patients and can lead to convulsions. Porphyria can exacerbate by several drugs, infectious processes, alcohol, and menstruation-induced hormonal-changes. Diagnosis is made by excess of urine porphobilinogen and 5-aminolaevulinic-acid. Treatment should include avoidance of precipitating factors and hemein infusions. Conclusions: SIADH is considered responsible for the hyponatremia seen in porphyria patients. Our patient showed an abnormal cortisol response to Insulin induced hypoglycemia, in accordance to (1) that demonstrated decreased output of cortisol and metabolites in porphyria patients secondary to decreased hemoproteins, as p450 cytochromes. Importantly, levels of endogenous hormones, particularly progesterone, can trigger an attack especially in luteal phase and in clomiphene citrate administration.1. Pozo et al Orphanet Journal of Rare Diseases 2014

Extended Use of Clomiphene Citrate in Induction of Ovulation in Polycystic Ovary Syndrome with Clomiphene Citrate Resistance

Background: Clomiphene citrate (CC) is still holding its place as the first-line treatment for induction of ovulation in polycystic ovary syndrome (PCOS) patients. Objective: to assess the effect of extended clomiphene citrate on pregnancy outcomes of clomiphene resistant PCOS. Patients and methods: this study was conducted on 48 PCO patients with CC resistance attended to the Obstetrics and Gynecology Outpatient Clinic at Menoufia University and Al-Bajour General Hospitals, from April 2018 to February 2020. Patients were treated with an extended CC administration (150 mg for 10 days) to overcome anovulation. Result: There was highly significant change in follicle-stimulating hormone (FSH), luteinizing hormone (LH) and FSH/LH after extended CC treatment (p < 0.001). Also, serum progesterone and number of follicles were significantly increased after treatment compared to before treatment. Conclusion: CC extended is a safe, effective with minimal side effect, but low pregnancy rate was observed. Therefore, further studies with large number of PCO patients with CC resistant with addition of other drugs are required to investigate the improvement of the pregnancy rate.

Extended Use of Clomiphene Citrate in Induction of Ovulation in Polycystic Ovary Syndrome with Clomiphene Citrate Resistance

Background: Clomiphene citrate (CC) is still holding its place as the first-line treatment for induction of ovulation in polycystic ovary syndrome (PCOS) patients. Objective: to assess the effect of extended clomiphene citrate on pregnancy outcomes of clomiphene resistant PCOS. Patients and methods: this study was conducted on 48 PCO patients with CC resistance attended to the Obstetrics and Gynecology Outpatient Clinic at Menoufia University and Al-Bajour General Hospitals, from April 2018 to February 2020. Patients were treated with an extended CC administration (150 mg for 10 days) to overcome anovulation. Result: There was highly significant change in follicle-stimulating hormone (FSH), luteinizing hormone (LH) and FSH/LH after extended CC treatment (p < 0.001). Also, serum progesterone and number of follicles were significantly increased after treatment compared to before treatment. Conclusion: CC extended is a safe, effective with minimal side effect, but low pregnancy rate was observed. Therefore, further studies with large number of PCO patients with CC resistant with addition of other drugs are required to investigate the improvement of the pregnancy rate.