Clomiphene Research Articles

Evaluation of effectiveness of Letrozole in treatment of infertility in women with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease, characterized by hyperandrogenism, oligomenorrhea, and polycystic ovaries. PCOS is one of the most causes that affect the women of childbearing age, and often leads to infertility. Various managements were proposed for infertile women with PCOS. However, the optimal management option has not been addressed satisfied. Although multiple treatments including weight reduction, clomiphene citrate, metformin, gonadotropins, and ovary cauterization have been reported to treat such condition, the efficacy still has insufficient evidence to support. Objectives: Purpose of this study was to evaluate the effectiveness of Letrozole in treatment of infertility in women with polycystic ovary syndrome. Materials & method: This study was carried out to assess the effectiveness of letrozole and on pregnancy outcomes including the ovulation induction, pregnancy rate, and endometrial thickness in infertile women with polycystic ovarian syndrome (PCOS). Total 106 infertile PCOS patients were recruited and allocated in two groups, Group-L (received letrozole at 2.5 mg twice daily on the 3rd–5th days of menstrual cycle for 5 consecutive days), Group-G 75 U/d−1 gonadotropin through intramuscular injection for 5 days starting from the third day of menstrual cycle). All patient in both arm completed treatment and follow-up. Patients in both groups were treated up to 5 treatment cycles. During follow up, transvaginalultrasonogram (TVS) was performed to see the details of the follicles and the endometrium. Data was processed and analysed with the help of computer program SPSS and Microsoft excel. Quantitative data expressed as mean and standard deviation and qualitative data as frequency and percentage. Comparison was done by tabulation and graphical presentation in the form of tables, pie chart, graphs, bar diagrams, histogram & charts etc. Result: Mean age of the patient was 26.3 ± 5.7 years in group-L and 25.9 ± 6.1 years in group-G. There were no statistical significant differences between the 2 groups regarding age, body weight, height, body mass index (BMI). Present study results showed that patients who received letrozole exert better outcomes in primary endpoint, including ovulation rate (86.7% in group-L & 62.2% in group-G, P =0.004), endometrial thickness (9.3 ± 1.1 mm in group-L & 8.5 ± 1.1 mm in group-G, P = 0.003) and pregnancy rate (64.1% in group-L & 30.1% in group-G, P =0.005). Abortion rate (till the end of 12th week) and multiple pregnancy rate were higher in group-G, but result were non-significant in between groups. Live birth rate in the letrozole group was higher 29(54.7%) than group-G 14(26.4%), the difference was statistically significant (P < .05). Conclusion: Patients who took Letrozole had significantly higher endometrial thickness than other group. Due to the higher pregnancy rate and lower incidence of abortion or multiple pregnancy, letrozole can be an effective for the treatment of anovulatory subfertility of the PCOS patients. Central Medical College Journal Vol 7 No 1 January 2023 Page: 13-19

Allium ampeloprasum var. Porrum (Alliaceae) Improves Metabolic and Reproductive Disorders Associated with Polycystic Ovary Syndrome in Wistar Rats.

To provide scientific evidence of the efficacy of Allium ampeloprasum against female infertility, the effects of the aqueous extract of the said plant (AE) were evaluated in rats with letrozole-induced polycystic ovary syndrome (PCOS). AE was administered orally to PCOS rats at doses of 192, 384, and 768 mg/kg. The positive control was co-treated with clomiphene citrate (1 mg/kg) and metformin (200 mg/kg). Normal and negative controls received distilled water. The vaginal contents of rats were examined daily under a microscope before (7 days) and during treatment. Treatments were administered orally for 15 days, and then, 6 rats from each group were sacrificed for biochemical and histological analyses. The remaining rats were mated with males of proven fertility for 5 days. The daily examination of vaginal smears allowed the evaluation of fertility index. After parturition, additional fertility parameters were determined. Results showed that in PCOS rats, AE decreased body weight (p < 0.001), abdominal fat weight (p < 0.001), serum levels of LH (p < 0.001), testosterone (p < 0.001), total cholesterol (p < 0.05), and LDL cholesterol (p < 0.01). HDL cholesterol increased and atherogenic indices decreased (p < 0.001). The number of Graafian follicles and corpora lutea increased, while cystic (p < 0.001) and atretic (p < 0.05) follicles decreased. AE also decreased oxidative stress in the ovaries, restored the estrous cycle, induced uterine epithelial cell hypertrophy, and improved fertility. These effects were attributed to phenols, flavonoids, terpenoids, and anthocyanins present in AE. The overall results justify the traditional use of A. ampeloprasum against female infertility and suggest its potential use as a dietary supplement for PCOS patients.

Iatrogenic and demographic determinants of the national plural birth increase

ObjectiveTo study the contribution of ovulation induction and ovarian stimulation, in vitro fertilization (IVF) and unassisted conception to the increase in national plural births in the U.S., a significant contributor to adverse maternal and infant health outcomes. DesignNational and IVF-assisted plural birth data were derived from the Centers for Disease Control and Prevention’s National Vital Statistics System (1967-2021, after introduction of Clomiphene Citrate in the U.S.) and the National Assisted Reproductive Technology Surveillance System (1997-2021), respectively. Main Outcome MeasuresIn addition to IVF-assisted plural births, the contributions of unassisted conception to plural births among women aged <35 and ≥35 years were estimated using plural birth rates from 1949-1966, and a Bayesian logistic model with race and age as independent variables. The contribution of ovulation induction and ovarian stimulation was estimated as the difference between national plural births and IVF-assisted and unassisted counterparts. ResultsFrom 1967-2021, the national twin birth rate increased 1.7-fold to a 2014 high (33.9/1000 live births), then declined to 31.2/1000 live births; the triplet and higher-order birth rate increased 6.7-fold to a 1998 high (1.9/1000 live births), then declined to 0.8/1000 live births. In 2021, the contribution of unassisted conception among women <35 to the national plural births was 56.1%, followed by ovulation induction and ovarian stimulation (19.5%), unassisted conception among women ≥35 (16.8%) and IVF (7.6%). During 2009-2021, the contribution of ovulation induction and ovarian stimulation has remained stable, the contribution of unassisted conception among women <35 and women ≥35 has increased, and the contribution of IVF has decreased. ConclusionOvulation induction and ovarian stimulation are leading iatrogenic contributors to plural births. They are, therefore, targets for intervention to reduce the adverse maternal and infant health outcomes associated with plural births. Maternal age ≥35 is a significant contributor to the national plural birth increase.

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

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

A Complete Overview of the Polycystic Ovarian Syndrome with Recent Advancement in Clinical Trial

Background: Polycystic ovarian syndrome (PCOS) has emerged as one of the most common endocrine and metabolic disorders seen in women of childbearing age throughout the whole world. The complex pathophysiology, different diagnostic criteria, and various manifestations attached to several environmental factors, including lifestyle influences, have made it one of the most difficult disorders to treat in recent times. In addition, inadequate knowledge among patients and a lack of dedicated approved medications have only enhanced the difficulties in treating such a heterogeneous disorder. Objective: The main objective of this review-type paper is to provide a detailed overview of PCOS along with the current concept of a clinical stance in this complex multigenic disorder. Method: The following databases were used for literature searches: PubMed, Frontiers, Science Direct, Springer, Wiley, and MDPI. For the purpose of finding pertinent articles and contents, the keywords “PCOS; hirsutism; psychological burden; obesity” and others of a similar nature were utilized. Conclusion: PCOS is a complicated hormonal, metabolic, and psychological condition with many different clinical manifestations. It is among the most prevalent causes of infertility. Before considering any medication choices, lifestyle modifications should be considered the primary therapeutic prescription for PCOS-related infertility. According to recent studies, PCOS does not affect the risk of ovarian or breast cancer, but it does raise the risk of endometrial cancer in women of all ages. These results suggest that PCOS may increase the risk of gynaecological cancer morbidity. The following stage is ovulation stimulation, which is best accomplished with letrozole and is followed by clomiphene citrate. Women who had not responded to the first-line oral ovulatory medicine were given gonadotropins as a backup. Early detection of girls with a high propensity to develop PCOS will be made possible by a comprehensive knowledge of the condition's etiology. Adolescent PCOS will be better managed overall, related comorbidities will be prevented, and quality of life will increase with customized therapeutic approaches.

Alternative treatment of polycystic ovary syndrome: pre-clinical and clinical basis for using plant-based drugs.

The most common cause of infertility and metabolic problems among women of reproductive age is polycystic ovary syndrome (PCOS), a multifaceted disorder. It is an endocrine disorder that occurs in approximately one in seven women. Among these PCOS patients, two thirds will not ovulate on a regular basis and seek treatment for ovulation induction. The symptoms vary in their severity, namely ovulation disorders, excessive androgen levels, or polycystic ovarian morphology. All these symptoms require a therapeutic approach. Many drugs are used to eradicate PCOS symptoms, like metformin, clomiphene citrate, spironolactone, and pioglitazone. Long-term treatment is required to achieve the desired outcome, which is often accompanied by significant adverse reactions. Some herbs and phytochemicals are equally effective for treating PCOS and produce minimal side effects. Recently, herbal products are gaining popularity due to their wide biological activities, safety, availability, and efficacy. The present review covers aetiology, current treatment, pathophysiology, and detailed pre-clinical and clinical studies on plants and phytochemicals that are proven to be useful for the treatment of symptoms associated with PCOS.

Protective effects of vanillic acid on letrozole-induced polycystic ovarian syndrome: A comprehensive study in female wistar rats

BackgroundPolycystic ovarian syndrome (PCOS) is one of the known causes of anovulatory fertility in the world. Previous research has linked oxidative stress could contribute to PCOS, and vanillic acid has shown antioxidant potential. Hence, the present study evaluated the effect of vanillic acid on letrozole-induced polycystic ovarian syndrome in female rats. Materials and methodsPCOS was induced in Wistar female rats with letrozole (1 mg/kg, orally) in carboxymethoxycellulose (1 % w/v), administered for 21 days. After induction, the standard group received clomiphene citrate (1 mg/kg, orally) while other treatment groups were administered with vanillic acid at doses 25, 50, and 100 mg/kg, orally for 15 days, and without treatment was considered a negative control group. Different parameters studied were body weight, ovary weight, blood glucose, lipid profile, hormonal levels [luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone], markers for oxidative stress (superoxide dismutase, reduced glutathione, catalase, and malonaldehyde), and histopathology of the ovary. Statistical analysis was done for the results and p < 0.05 was considered to indicate the significance. ResultsVanillic acid-treated animals showed a concentration-dependent activity on the tested parameters. The highest tested dose (100 mg/kg) produced a more prominent effect in significantly (P < 0.001) decreasing the body weight, and ovary weight and improving the hormonal imbalance. Also, vanillic acid significantly (P < 0.01) reduced elevated blood sugar and lipid levels. Additionally, vanillic acid reduced oxidative stress significantly (P < 0.001) in the ovaries of female rats. Histopathological reports showed a reduction in cystic follicles and appearance of normal healthy follicles at different stages of development after the administration of vanillic acid. Furthermore, these effects were observed to be comparable with those recorded for standard drug, clomiphene. ConclusionThe current study data suggests that vanillic acid has protected the letrozole-induced polycystic ovarian syndrome. In the event of several side effects associated with conventional treatments used for PCOS, the findings of this study suggest the promising role of vanillic acid. More research in this direction might identify the true potency of vanillic acid in the treatment of PCOS.

Comparative study of the efficacy of combined metformin–clomiphene citrate versus combined metformin–letrozole in induction of ovulation in overweight women with polycystic ovarian syndrome

Background Polycystic ovary syndrome (PCOS) is the common cause of infertility. Clomiphene citrate (CC) is the first-line treatment in ovulation induction. Metformin biguanide has been used in insulin resistance in PCOS women. Adding metformin to CC in the CC-resistant PCOS was highly effective in achieving ovulation in 68.6–77.7% of patients. Letrozole, aromatase inhibitor, its use in patients with CC-resistant PCOS achieved ovulation 54.6–84.4% of the time. Aim We aimed to compare the efficacy of combined metformin–CC to combined metformin–letrozole in ovulation induction in overweight infertile PCOS women. Patients and methods A prospective randomized study was conducted at Obstetrics &amp; Gynecology Department in Tanta University Hospitals. In total, 40 infertile overweight cases with PCO were included. Cases were randomly allocated in two groups. Results The mean age was 26.40 ± 5.20 years for CC group and 26.50 ± 5.10 years for letrozole group. BMI was 27.50 ± 1.43 for CC group and 27.45 ± 1.36 for letrozole group. The duration of infertility was 2.90 ± 1.40 years for CC group and 2.88 ± 1.21 for letrozole group. There was insignificant difference in both groups as regards the follicles more than 18 mm and endometrial thickness. But, as regards progesterone level, there was a statistically significant increase in letrozole group than CC group (P&lt;0.005). Concerning pregnancy rate, there was insignificant difference between two groups. Conclusion The present investigation demonstrated that both CC and letrozole are similarly viable in treatment of infertility in PCOS patients, when joined with metformin treatment.

Clomiphene citrate vs Letrozole as first line ovulation induction drug in infertile PCOS women

Background: Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy resulting in anovulatory infertility in young women as in recent years have seen a significant rise in women presenting with PCOS . Despite wide acceptance of clomiphene citrate (CC) as the first-line drug for ovulation induction in women with polycystic ovaries (PCOS), a significant proportion of women do not respond to this treatment. In addition, CC use is known to have several disadvantages, including a discrepancy between ovulation and conception rates. Recent studies have suggested that letrozole, an aromatase inhibitor, can be used for ovulation induction and is associated with higher pregnancy rates and less complications than CC treatment in women with PCOs.

Mathematical study of polycystic ovarian syndrome disease including medication treatment mechanism for infertility in women.

Among women of reproductive age, PCOS (polycystic ovarian syndrome) is one of the most prevalent endocrine illnesses. In addition to decreasing female fertility, this condition raises the risk of cardiovascular disease, diabetes, dyslipidemia, obesity, psychiatric disorders and other illnesses. In this paper, we constructed a fractional order model for polycystic ovarian syndrome by using a novel approach with the memory effect of a fractional operator. The study population was divided into four groups for this reason: Women who are at risk for infertility, PCOS sufferers, infertile women receiving therapy (gonadotropin and clomiphene citrate), and improved infertile women. We derived the basic reproductive number, and by utilizing the Jacobian matrix and the Routh-Hurwitz stability criterion, it can be shown that the free and endemic equilibrium points are both locally stable. Using a two-step Lagrange polynomial, solutions were generated in the generalized form of the power law kernel in order to explore the influence of the fractional operator with numerical simulations, which shows the impact of the sickness on women due to the effect of different parameters involved.

Comparison between Clomiphene Citrate / Metformin Stair Step Protocol and Traditional Protocol in Treatment of Polycystic Ovary

Comparison between Clomiphene Citrate / Metformin Stair Step Protocol and Traditional Protocol in Treatment of Polycystic Ovary

Determinant Factors for Ongoing Pregnancy in Homologous Intrauterine Insemination Cycles - A Prospective Study.

Intrauterine insemination (IUI) is the most common assisted-reproduction treatment. However, it has lower success rate in comparison to other treatments. Therefore, determining factors that contribute to IUI success is of particular interest and this was the purpose of this prospective study. In this study, only homologous inseminations with fresh semen samples were included. All women received mild ovarian stimulation with clomiphene citrate and gonadotropins. Before IUI, basic semen analysis, evaluation of DNA fragmentation index (DFI), as well as measurement of sperm redox potential, were performed on each semen sample. Semen was processed with density-gradient centrifugation and 500 μl of processed sperm was used for insemination. In 200 cycles, there were 36 pregnancies, six of them ectopic. Cycles with ongoing pregnancies were characterized by younger male and female age and higher number of follicles. Multivariate logistic regression analysis showed that only female age was significantly associated with ongoing pregnancy. DFI was positively correlated with male age and negatively correlated with sperm concentration and progressive motility. Semen redox potential showed a strong negative correlation with sperm concentration and positive correlation with DFI. Female age seems to be the most important determinant factor for the achievement of an ongoing pregnancy in homologous IUI cycles with fresh semen.

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

Suspected case of erythema multiforme major caused by combination therapy of glimepiride, voglibose, and metformin with clomiphene citrate in a polycystic ovary syndrome and type 2 diabetes patient in India

Suspected case of erythema multiforme major caused by combination therapy of glimepiride, voglibose, and metformin with clomiphene citrate in a polycystic ovary syndrome and type 2 diabetes patient in India

Laparoscopic Ovarian Drilling in Women with Anovulatory Infertility

Background: Polycystic ovaries are common condition mostly found in reproductive aged women. Conventionally clomiphene is used instead of letrozole as first line drug in patients presenting with infertility as later is off label. 20% women are clomiphene resistant, those can be treated with gonadotrophins, other ovulation induction drugs or laparoscopic ovarian drilling. Objective: As PCOS is one of the leading cause of anovulatory infertility among women of reproductive age group. We study different factors to speculate the effect of laparoscopic ovarian drilling. Study Design: Quasi experimental study. Setting: Department of Gynecology &amp; Obstetrics, Faisalabad Medical University, Faisalabad Pakistan. Duration: One year from August 2021 to August 2022. Methods: Our study includes 100 anovulatory PCOS patients resistant to conceive by medical treatment like clomiphene, later selected for LOD. Various clinical and biochemical parameters of PCOS were examined. Outcome was measured between different categories by using SPSS V 25 system. Results: Polycystic anovulatory women with BMI &gt;35kg/m2, serum testosterone concentration &gt; 4.5 and span of infertility &gt; 3 years showed lack of response to LOD. Whereas response was seen in patients with less BMI and testosterone concentration along with decrease span of infertility. Conclusion: Ovarian drilling by laparoscopy is an efficient second choice for infertile anovulatory patients resistant to clomiphene citrate, main benefits are single time treatment, as opposed to several trials of ovulation induction, cost effective and a method to replace gonadotrophins effectively for ovulation induction while maintaining pregnancy rate.

Effect of Coenzyme Q10a and Clomiphene Citrate for Ovulation Induction in Patients with PCOS as Compared to Clomiphene Citrate alone

To evaluate the effects of coenzyme Q10A and clomiphene citrate taken in addition to other drugs to stimulate ovulation in people with polycystic ovarian syndrome. The Department conducted the study of Obstetrics and Gynecology, Pakistan Ordinance Factory (POF), Wah Cantonment, Rawalpindi from Mar 2019 to Feb 2021 By using a lottery, all of the patients were split into two random groups. Group A was given Coenzyme Q10A 60mg daily from day 1 of the cycle thrice a day and clomiphene citrate 150mg/day from days 2-6 of the cycle, and Group B was given only clomiphene citrates 150mg/day from 2-6 day of cycle for 5 days. The follicular growth and maturation were observed on days 10, 12, and 14 of the cycle with transvaginal ultrasound. Ovulation was confirmed by measuring serum progesterone level on day 21 of the cycle. Patients were followed for 3 cycles.The mean number of mature follicles in Group A was 1.63+0.49 and 1.3+0.47 in Group B (p-value=0.01). The analysis of either of the groups' ovulation statuses revealed that in 70% of patients (n=21) in Group A and 36.67% (n=11) in Group B, ovulation was initiated (p value= 0.01). We concluded that the outcome of combined coenzymeQ10A and clomiphene citrate is significantly better for patients with polycystic ovarian syndrome; inducing ovulation is more effective with clomiphene citrate alone.

Trazodone associated with Clomiphene a proposal treatment for post finasteride syndrome

Erectile dysfunction caused by medications are probably caused by the disconnection of synaptic circuits responsible for linking libido to erection. For instance, it is well known that sexual dysfunction may occur in patients treated with finasteride, an inhibitor of the enzyme 5alpha-reductase, prescribed for androgenetic alopecia and benign prostatic hyperplasia. Interestingly, sexual dysfunction persists after drug discontinuation. Clomiphene citrate is a selective estrogen receptor modulator that has been used for the treatment of hypogonadism in men. It acts centrally to increase secretion of luteinizing hormone. Trazodone is a multifunctional drug with hypnotic actions at low doses due to blockade of 5-HT2A receptors, as well as H1 histamine receptors and α1 adrenergic receptors, therefore this drug can cause severe priapism and in many cases causing penile necrosis or permanent loss of erectile function. Therefore, we propose that trazodone and clomiphene can restore libido synaptic circuits, thus these associated drugs can be a treatment for post-finasteride syndrome.

SPERM PARAMETERS' PREDICTIVE VALUE IN INTRAUTERINE INSEMINATION SUCCESS: A SINGLE-CENTER EXPERIENCE

Although intrauterine insemination is a widely used assisted reproductive technique there is no consensus on sperm parameters that affect the probability of pregnancy. Therefore, the purpose of this study was to determine whether semen parameters affect intrauterine insemination success. A total of 403 couples (345 negative pregnancies, and 58 positive pregnancy) that underwent 549 intrauterine insemination treatment cycles for heterogenous indications were included in the study. Clomiphen citrate, letrazole and/or gonadotropins were used for ovarian stimulation in women in this study. The spermiogram tests of the spouse of receiving IUI tretment were examined. Clinical pregnancy occurred in 58 of 549 intrauterine insemination (10.56%). Unexplained infertility, polycystic ovary syndrome, and cervical-tubal factors were higher in positive pregnancy group compared to negative pregnancy group while male factor was more prevalant in negative pregnancy group comparison to positive pregnancy group (p=0.03). There was no statistical difference between women with positive and negative pregnancy in terms of age (≤ 35 and &gt; 35), body mass index, infertility type, infertility time, endometrial thickness on HCG day, stimulation protocol, cycle numbers, number of insemination, estradiol, prolactin, LH, FSH, and TSH levels (p&gt;0.05). The sperm characteristics in males [ejaculate volum, sperm concentration, total sperm count, motility, immotility, and total progressive motile sperm count] did not significantly differed between positive and negative pregnancy groups (p&gt;0.05).&#x0D; Briefly, the present study found that the conception probability of intrauterine insemination did not correlate with the spermiogram parameters.

Protective Effects of Chia Seeds and Omega-3 Fatty Acid against Cyclophosphamide-Induced Oligospermia in Male Wistar Rats: Potential Risks of Adverse Drug Interaction with Chia Seeds.

Objectives: The aim of this study was to investigate whether chia (Salvia hispanica) seeds, which are rich in omega-3 fatty acids, amino acids, and vitamins with antioxidant properties, can mitigate the negative effects on male reproductive function caused by cyclophosphamide, a frequently used chemotherapeutic agent. Methods: Male wistar rats are divided into seven groups (n=6). All groups except the normal control (NC) received cyclophosphamide (30mg/kg, i.p.) for the first 5 days. The standard group received clomiphene citrate (0.25 mg/kg, p.o.). Treatment groups T1%, T5%, T10%, and ω-3 received 1%, 5%, and 10% chia seeds in the diet, and 880 mg/kg omega-3 fatty acid (p.o) respectively for 15 days. The effect on the reproductive system was evaluated by analysis of epididymal sperm characteristics, biochemical parameters, and serum testosterone level. Results: Clomiphene citrate improved oligospermia via hormone mediated effect. Chia seeds and omega-3 fatty acid treatment also showed improvement in reproductive parameters including oxidative stress and histological features of the testes. Omega-3 fatty acid treatment was more effective for the prevention of cyclophosphamide toxicity on testes as compared to chia seeds. Nasal bleeding was noted in several animals subjected to chia seed treatment. This occurrence might be attributed to chia seeds' impact on coagulation and/or platelet function, potentially heightened due to chemotherapy associated bone marrow suppression. Conclusions: In our study, chia seeds as well as omega-3 fatty acid treatment were found to be protective against cyclophosphamide-induced reproductive toxicity in rats. However, the adverse effect of hemorrhage associated with drug interaction of chia seeds with cytotoxic chemotherapeutic drugs needs careful attention and further investigation.

Clomiphene Citrate a First Step to Improve Idiopathic Male Infertility: A Retrospective Analysis

Background. Infertility in men is a common and worldwide problem with limited registered treatment options and licensed therapies. Clomiphene citrate (CC) is an empirical off-label therapy. CC is a selective estrogen receptor modulator that may improve testicular function, including sperm quality, by stimulating steroidogenesis and spermatogenesis. However, there is a lack of evidence regarding the efficacy of CC as therapy for male infertility. Objectives. To assess the improvement of CC on sperm parameters, pregnancy, hypogonadism, and measurement of safety. Methods. In this retrospective study, 52 men treated with CC for idiopathic nonobstructive infertility were analyzed. Data of sperm parameters, pregnancy rate, hormonal values, side effects, improvement in hypogonadal symptoms, and potential predictors of treatment response were collected. Results. A total of 52 infertile men underwent CC treatment. An increase in sperm concentration was observed in 19 patients (37%). An upgrade in sperm concentration classification according to the WHO criteria was noted in 21% of the patients receiving CC therapy. Additionally, 15% of initially ineligible patients for intrauterine insemination became eligible during CC. In total, 33% of couples achieved pregnancy, either spontaneously or with assisted reproductive techniques (ART). Low-normal follicle-stimulating hormone and larger testis volume before CC treatment were predictors for better semen concentration during treatment. The retrieval rate was 75% for azoospermic patients who underwent testicular sperm extraction or percutaneous epididymal sperm aspiration, enough for intracytoplasmic sperm injection. With CC, testosterone levels increased and hypogonadal symptoms improved. Mild side effects were reported by 8% of patients. Conclusion. The results of this study contribute to the existing evidence that CC is a safe and noninvasive therapy for idiopathic infertile males. It could be considered as a step-up therapy before initiating more invasive ART procedures.