Clomiphene Citrate For Induction Research Articles

Clomiphene Citrate versus Letrozole for Induction of Ovulation in Infertile women having Polycystic Ovarian Syndrome (Randomized Controlled Trial)

Background: Polycystic ovary syndrome is a disorder but with unclear etiology that its diagnosis depends on exclusion of other etiologies with ovulatory disorders and androgen excess as congenital adrenal hyperplasia, 21-hydroxylase deficient non classic congenital adrenal hyperplasia (NCAH), adrenal or ovarian androgen-secreting tumors, disorders of adrenocortical dysfunction as Cushing’s disease, and abuse of androgenic or anabolic drugs. Polycystic ovary syndrome affects approximately 6-15% of women in reproductive age and constitutes 50% of the causes of infertility in women. Aim of the Work: To compare the efficacy of letrozole on ovulation induction to that of clomiphene citrate in women suffering polycystic ovary syndrome and the effect on the follicular maturation, endometrial thickness and pregnancy rate. This study was carried in the outpatient infertility clinic of Ain-Shams Maternity Hospital during the period from November 2020 till April 2021. Patients and Methods: This study included 80 infertile women diagnosed as having polycystic ovary syndrome. Women were randomized into two groups. Letrozole group (1) included 40 women who were given the aromatase inhibitor (Letrozole) orally in a 5mg dose daily from day 3 to day 7 of the menstrual cycle. While Clomiphene citrate group (2) included 40 women who were given the clomiphene citrate orally in 100mg dose daily from day 3 to day 7 of the menstrual cycle. All women were counseled and informed consent was obtained before recruitment. Results: In this study, ovulation rate was significantly more frequent in the Letrozole group (82.5%, 33 women reached ovulation successfully) than in Clomiphene citrate group (60%, 24 women reached ovulation successfully) within P value=0.024. Clomiphene citrate at a dose of 100mg showed more efficacies in the number of follicle ≥18mm than Letrozole at a dose of 5mg. In Letrozole group, the number of follicles (≥18mm in diameter) ranged from 1 to 2 with a Mean±SD= 1.4±0.65 and in Clomiphene citrate group, the number of follicles (≥18mm in diameter) ranged from 1 to 3 with a Mean±SD= 1.9± 0.41 (P value=0.0001). Conclusion: Letrozole can be considered as a first line treatment of anovulation in polycystic ovary syndrome. But, moreover studies including larger number of cases will further confirm the efficacy of letrozole versus clomiphene citrate in induction of ovulation, reaching to the optimum doses for aromatases inhibitors, more observation on endometrial thickness, incidence of pregnancy outcomes, incidence of abortion and incidence of congenital fetal malformations.

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.

Comparison of Tamoxifen and Clomiphene Citrate for Ovulation Induction in Women with Polycystic Ovarian Syndrome: A Prospective Study.

Background:The purpose of this study was to compare the efficacy of tamoxifen and clomiphene citrate in induction of ovulation in women with PCOS and anovulation.Methods:In this prospective cohort study, 104 women with PCOS and primary infertility were enrolled after fulfilling the inclusion and exclusion criteria. The patients were allocated in two groups; group A (n=54) received tamoxifen 40 mg once daily (Days 3–7) and group B (n=50) received clomiphene citrate 100 mg once daily (Days 3–7). Serial ultrasounds were done till the administration of human chorionic gonadotropin (hCG). The ovulation and pregnancy rates in both groups were compared. The number of dominant follicles, estradiol levels, and endometrial thickness were also studied. Comparison was done using chi-square and student’s t-test and a p-value of less than 0.05 was considered statistically significant.Results:The number of dominant follicles and serum estradiol levels were significantly higher in group B (p<0.05), whereas the endometrial thickness was significantly more in group A (p<0.05). The ovulation rates were similar in both groups (66.6% vs. 70%, p=0.715). Pregnancy rate per treatment cycle and per ovulatory cycle was marginally higher in group A (14.81% and 22.22%, respectively), as compared to group B (14% and 20%, respectively), but the difference was not statistically significant (p>0.05).Conclusion:Tamoxifen and clomiphene citrate are both equally effective in induction of ovulation and achieving a pregnancy in women with PCOS.

A Comparative Study Between Clomiphene Citrate and Tamoxifen for induction of Ovulation in Women Complaining of Polycystic Ovary Syndrome

PCOS is the most common endocrine disorder among women between the ages of 18 and 44. It affects approximately 2% to 20% of this age group depending on how it is defined. PCOS is due to a combination of genetic and environmental factors. Objective: To compare the efficacy of Clomiphene citrate and Tamoxifen induction of ovulation women with polycystic ovary syndrome. Patients and Methods: This clinical trial study was conducted at Al-Husien Hospital from June 2019 to December 2019 after approval of the research ethics committee, on 100 patients with P.C.O. The participants were recruited from women attending the outpatient infertility clinic of Al-Husien Hospital.Patients are classified randomly into 2 groups: Group A: 50 patients (clomiphene Group). Group B: 50 patients (tamoxifene Group).Results: Ovulation rate was significantly better under tamoxifen therapy. Pregnancy rate was significantly better under tamoxifen therapy. Number of stimulated follicles was not significantly different between the two drugs.Endometrial thickness was significantly better under tamoxifen therapy both preovulatory and midluteal. Endometrial perfusion volume (EV), Vascularization index (VI), and Vascularization flow index (VFI) were significantly better under tamoxifen therapy. Adverse effects with thetwo drugs were non-significant. Endometrialperfusion indices weresignificantly better pregnant versus non-pregnantcases.Conclusion:Tamoxifen can give similar or even better results than clomiphene citrate induction of ovulation women with PCOS. Each of them can be used as a first line option for induction of ovulation women with PCOS in selected cases.

Clomiphene citrate plus cabergoline versus clomiphene citrate for induction of ovulation in infertile euprolactinemic patients with polycystic ovary syndrome: A randomized clinical trial

Abstract Objective To compare the effect of adjunctive use of cabergoline with clomiphene citrate (CC) in infertile polycystic ovarian syndrome (PCOS) patients with normal prolactin level. Study design A randomized clinical trial (NCT 02644304). Setting Assiut University Hospital, Assiut, Egypt. Materials and methods Infertile euprolactinemic PCOS patient were recruited and randomized in a 1:1 ratio to CC plus cabergoline or CC alone. All patients were evaluated by ultrasound examination for number, size of ovarian follicles and they were followed up for 3 consecutive cycles. The primary outcome of the study was the cumulative rate of ovulation in both groups allover the 3 cycles of treatment. The secondary outcomes included clinical pregnancy rate, miscarriage rate, multiple pregnancy rate, ovarian hyperstimulation rate and the rate of adverse effects of the study medications. Results One-hundred thirty patients were included (65 in each group). No statistical difference between both groups regarding the basal criteria. The cumulative ovulation rate in the CC plus cabergoline group was 76.7% versus 58.3% in the CC group (p = .032). Additionally, the largest follicle size in each cycle was significantly more in the CC plus cabergoline group (p Conclusions The use of cabergoline with CC in induction of ovulation in euprolactinemic infertile women with PCOS results in high ovulation rate, high pregnancy rate as compared to use of CC alone.

Effect of estradiol valerate on the pregnancy rate in patients receiving letrozole for induction of ovulation

Abstract Background Letrozole is as effective as clomiphene citrate for induction of ovulation in patients with PCOS. Adequate endometrial development is required for pregnancy to occur, and pregnancy rates were found to be higher when the endometrium reached at least 10 mm thickness. Objective To study the effect of estradiol valerate on the endometrial thickness and subsequently the pregnancy rate in PCOS cases receiving letrozole for induction of ovulation as compared to letrozole alone. Study design A randomized controlled study. Setting was at the infertility clinic of the Cytogenetic and Endoscopy Unit, Zagazig University Hospital. Material and methods The study included 273 patients who underwent ovulation induction and timed intercourse. Patients were divided into 2 groups: controlled ovarian stimulation was done in group 1 by letrozole with addition of estradiol valerate and in group 2 by letrozole alone. Results As regard the clinical pregnancy rate, we found a statistically significant difference between the 2 studied groups, with documented clinical pregnancy in 34 patients in group 1 compared to only 16 patients in group 2. Conclusion This study showed that the pregnancy rate achieved with letrozole/estradiol valerate combination was significantly higher than with letrozole alone. This was attributed to the improvement of endometrial thickness by estradiol valerate.

Role of Letrozole Versus Clomiphene Citrate in Induction of Ovulation in Patients with Polycystic Ovarian Syndrome

Objective: the aim of this work is to compare the effect of Letrozole versus Clomiphene citrate (CC) in induction of ovulation in Polycyctic ovarian syndrome (PCOS) patients. Patients and methods: The study was conducted in Al Maadi Military Hospital at the department of Obstetrics and Gynecology (out-patient infertility clinic). The study is a prospective randomized study consisting of 100 Egyptian patients diagnosed as having PCOS. Patients were divided into two groups with randomization sheet and allocation concealment: Group (A): includes 50 females taking Letrozole 5mg tab orally once daily started in day 3 to day 7 of menstrual cycle for 3 cycles. Group (B): includes 50 females taking Clomiphene Citrate 100mg tab orally once daily started day 3 to day 7 of menstrual cycle for 3cycles. Trans-vaginal ultrasound was done from day 9-11 of the cycle to document ovulation rate, endometrial thickness and number of follicles and from day 14 (mid cycle day) to evaluate the target size of the follicle (18-22mm) and to assess the need to HCG administration. Results: Letrozole is significantly higher regarding endometrial thickness (Let 9.2mm Vs CC 8.0mm) and pregnancy rate (Let 48% Vs CC 28%), while Clomiphene Citrate (CC) is significantly higher regarding number of follicles (48%) as it produces multiple number of follicles compared to Letrozole (26%) which produces mono-follicle only. Both drugs are significantly similar regarding the ovulation rate. The study concluded that Letrozole can be used as first line therapy for induction of ovulation in polycystic ovary syndrome patients. Conclusion: The pharmacodynamics of Letrozole (does not deplete ERs, short half-life, keeps intact hypothalamic pituitary axis) ensures improved endometrial thickness and cervical mucus and monofollicular ovulation. Therefore, these factors may lead to a higher pregnancy rate and greater likelihood of singleton pregnancy.

Role of Letrozole Versus Clomiphene Citrate in Induction of Ovulation in Patients with Polycystic Ovarian Syndrome

Objective: the aim of this work is to compare the effect of Letrozole versus Clomiphene citrate (CC) in induction of ovulation in Polycyctic ovarian syndrome (PCOS) patients. Patients and methods: The study was conducted in Al Maadi Military Hospital at the department of Obstetrics and Gynecology (out-patient infertility clinic). The study is a prospective randomized study consisting of 100 Egyptian patients diagnosed as having PCOS. Patients were divided into two groups with randomization sheet and allocation concealment: Group (A): includes 50 females taking Letrozole 5mg tab orally once daily started in day 3 to day 7 of menstrual cycle for 3 cycles. Group (B): includes 50 females taking Clomiphene Citrate 100mg tab orally once daily started day 3 to day 7 of menstrual cycle for 3cycles. Trans-vaginal ultrasound was done from day 9-11 of the cycle to document ovulation rate, endometrial thickness and number of follicles and from day 14 (mid cycle day) to evaluate the target size of the follicle (18-22mm) and to assess the need to HCG administration. Results: Letrozole is significantly higher regarding endometrial thickness (Let 9.2mm Vs CC 8.0mm) and pregnancy rate (Let 48% Vs CC 28%), while Clomiphene Citrate (CC) is significantly higher regarding number of follicles (48%) as it produces multiple number of follicles compared to Letrozole (26%) which produces mono-follicle only. Both drugs are significantly similar regarding the ovulation rate. The study concluded that Letrozole can be used as first line therapy for induction of ovulation in polycystic ovary syndrome patients. Conclusion: The pharmacodynamics of Letrozole (does not deplete ERs, short half-life, keeps intact hypothalamic pituitary axis) ensures improved endometrial thickness and cervical mucus and monofollicular ovulation. Therefore, these factors may lead to a higher pregnancy rate and greater likelihood of singleton pregnancy.

Long-term use of clomiphene citrate in induction of ovulation in PCO patients with clomiphene citrate resistance

ObjectiveThe aim of our study to evaluate the effect of extended clomiphene citrate treatment on the ovulation rate, pregnancy rate, and hormonal profile of clomiphene resistant PCOS. MethodologyThis a prospective study conducted in Maternity Hospital Minia University, 200 patients with PCOS recruited in the study during the period from September 2015 till February 2016 (6 months was duration of the study), they were diagnosed as PCO with clomiphene resistance before being recruited in the study. They received 150mg clomiphene citrate for 10 days start in 2nd day of cycle for three consecutive cycles, and followed up for another three months without treatment, last follow-up cycle was on February. We studied the effect of extended treatment with CC in ovulation rate, pregnancy rate and hormonal profile in patients before and after treatment. ResultsThere was significant improvement in ovulation rate in the patients after extended CC treatment for 3 months and 3 months follow-up (as 12 cases in the first cycle and 32 cases in the second cycle and increased to 76 cases in the third cycle) while no ovulation documented before treatment pregnancy rate was 17% itis generally low but it highly significant when compared with was zero preceding treatment. ConclusionExtended CC treatment is good method to improve ovulation and pregnancy rate in CC resistant PCOS but further multi-center studies are needed to provide more powerful evidence.

Clomiphene Citrate for Induction of Ovulation in Women with Unexplained Infertility

Clomiphene Citrate for Induction of Ovulation in Women with Unexplained Infertility

The adjuvant effect of metformin and N-acetylcysteine to clomiphene citrate in induction of ovulation in patients with Polycystic Ovary Syndrome

Objectives: To assess the adjuvant effect of metformin and N-acetylcysteine (NAC) to clomiphene citrate (CC) in induction of ovulation in Polycystic Ovary Syndrome (PCOS) patients.Study design: 120 women with PCOS were randomly divided into three equal groups: group I received CC only, group II received CC plus NAC and group III received CC plus metformin.Results: There was a significant difference between group II and other two groups regarding average number of ovulatory follicles >18 mm (2.25 versus 1.75 and 1.89, respectively), but no significant difference between the three study groups regarding number of intermediate follicles 14–18 mm (4, 10 and 4, respectively). There was no significant difference between the three study groups regarding occurrence and laterality of ovulation, pregnancy rate per cycle but a significant difference between group II and other two groups regarding pregnancy rate per patient (20% versus 10% and 10%, respectively, p value 0.05). There was a highly statistically significant difference between group II and other two groups regarding peak endometrial thickness (7.3 ± 1.1 versus 5.4 ± 0.6 and 5.3 ± 0.6, respectively).Conclusions: NAC as an adjuvant to CC for induction of ovulation improves ovulation and pregnancy rates in PCOS patients with beneficial impacts on endometrial thickness.

Combined pioglitazone–metformin and clomiphene citrate versus metformin and clomiphene citrate in induction of ovulation in women with clomiphene citrate-resistant polycystic ovary syndrome

To compare the efficacy of pioglitazone + metformin and clomiphene citrate (CC) with metformin and CC in women with CC-resistant polycystic ovary syndrome (PCOS). Randomized clinical trial (RCT). A university teaching hospital in Cairo, Egypt. One hundred women with CC-resistant PCOS. Fifty women received pioglitazone 15 mg + metformin 850 mg once daily from the first day of the cycle for 10 days, and 50 women received metformin (500 mg three times daily). Clomiphene citrate 100 mg from the third day of the cycle for 5 days was added to each group. Treatment was continued for three cycles. Ovulation rate and pregnancy rate. Ovulation rate was significantly higher in the pioglitazone + metformin and CC group than the metformin and CC group (69.8% versus 48.8%) ( p : 0.002). Significantly higher serum E 2 on day 12 and thicker endometrium were found in the pioglitazone + metformin and CC group in the three follow up cycles. Also, cummulative pregnancy rate was significantly higher in the pioglitazone + metformin and CC group than the metformin and CC group (58% versus 34%) ( P : 0.027). The use of pioglitazone/metformin and CC is more effective than metformin and CC as regards ovulation and pregnancy rates in anovulatory women with CC-resistant PCOS.

N‐acetylcysteine as an adjuvant to clomiphene citrate for successful induction of ovulation in infertile patients with polycystic ovary syndrome

The aim of this study was to evaluate the effect of oral N-acetylcysteine (NAC) administration as an adjuvant to clomiphene citrate (CC) on induction of ovulation outcomes in patients with polycystic ovary syndrome (PCOS). In this placebo-controlled double-blind randomized clinical trial, 180 PCOS infertile patients were randomly divided into two groups for induction of ovulation. Patients in group 1 received CC 100 mg/d plus NAC 1.2 g/d and patients in group 2 received CC plus placebo for 5 days starting at day 3 of the cycle. On the 12th day of the menstrual cycle in the presence of at least one follicle with an 18-20-mm diameter in ultrasound evaluation, 10,000 U hCG was injected intramuscularly and timed intercourse was advised 36 h after hCG injection. Serum β-hCG level was measured on the 16th day after hCG injection. The number of follicles >18 mm and the mean endometrial thickness on the day of hCG administration were significantly higher among the CC+NAC group (P-value = 0.001). The ovulation and pregnancy rates were also significantly higher in the CC+NAC group (P-value = 0.02 and 0.04, respectively). No adverse side-effects and no cases of ovarian hyperstimulation syndrome were observed in the group receiving NAC. NAC as a safe and well-tolerated adjuvant to CC for induction of ovulation can improve the ovulation and pregnancy rates in PCOS patients. It may also have some beneficial impacts on endometrial thickness.

A prospective randomized trial comparing the efficacy of Letrozole and Clomiphene citrate in induction of ovulation in polycystic ovarian syndrome

OBJECTIVES:To compare the efficacy of letrozole and clomiphene citrate (CC) in patients of anovulatory polycystic ovarian syndrome (PCOS) with infertility.MATERIALS AND METHODS:This prospective randomized clinical trial included 204 patients of PCOS. 98 patients (294 cycles) received 2.5–5 mg of letrozole; 106 patients (318 cycles) received 50–100 mg of CC (both orally from Days 3–7 of menstrual cycle). The treatment continued for three cycles in both the groups. Main outcome measures: ovulation rate, endometrial thickness, and pregnancy rate. Statistical analysis was done using SPSS 13 software. P value less than 0.05 was considered significant.RESULTS:The mean number of dominant follicles in letrozole groups and CC groups was 1.86±0.26 and 1.92±0.17, respectively (P=0.126). Number of ovulatory cycle in letrozole group was 196 (66.6%) versus 216 (67.9%) in CC group (P=0.712). The mean mid-cycle endometrial thickness was 9.1±0.3 mm in letrozole group and 6.3±1.1 in CC group, which was statistically significant (P=0.014). The mean Estradiol [E2] level in clomiphene citrate group was significantly higher in CC group (364.2±71.4 pg/mL) than letrozole group (248.2± 42.2 pg/mL). 43 patients from the letrozole group (43.8%) and 28 patients from the CC group (26.4%) became pregnant.CONCLUSION:Letrozole and CC have comparable ovulation rate. The effect of letrozole showed a better endometrial response and pregnancy rate compared with CC.

Adding phytoestrogens (Cimicifugae racemosae) to clomiphene citrate induction cycles in polycystic ovary women raises pregnancy rates – A randomized trial

Adding phytoestrogens (Cimicifugae racemosae) to clomiphene citrate induction cycles in polycystic ovary women raises pregnancy rates – A randomized trial

Letrozole versus Clomiphene Citrate for Induction of Ovulation in Patients with Polycystic Ovarian Syndrome Undergoing Intrauterine Insemination

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women in the reproductive age group, and is one of the most common causes of hyperandrogenic anovulatory infertility. The aromatase inhibitor, letrozole, has been used for induction of ovulation. The purpose of this study was to compare the effects of letrozole and clomiphene citrate in induction of ovulation among patients with PCOS undergoing intrauterine insemination.MethodsIn a double-blind randomized study, 60 infertile patients with PCOS received standard doses of either clomiphene citrate or letrozole as an induction protocol prior to intrauterine insemination. A hormonal profile, pelvic ultrasound, hysterosalpingogram, and/ or laparoscopy were done for all patients. The patients were monitored for ovulation by translational ultrasonographic folliculometry, with measurement of number and size of the follicles, as well as endometrial thickness. Human chorionic gonadotrophin (HCG) was injected intramuscularly when at least one mature follicle ≥18 mm diameter was detected, and intrauterine insemination was performed 32–36 hours later. Transvaginal ultrasound and β-HCG measurement were performed for confirmation of pregnancy.ResultsLetrozole and clomiphene citrate achieved follicle maturation within a mean ± standard deviation (SD) of 13.2 ± 1.53 and 14.1 ± 1.35 days, respectively, showing no significant difference (P > 0.05). The mean number of follicles reaching ≥18 mm on the day of HCG administration was significantly higher in patients who received clomiphene citrate (2.9 ± 1.77) than in those receiving letrozole (1.2 ± 0.9). Letrozole had a significantly greater effect than clomiphene citrate on endometrial thickness (9.16 ± 1.36 versus 4.46 ± 1.71). The number of pregnancies achieved in the letrozole group was significantly (P < 0.05) greater than in the clomiphene group.ConclusionLetrozole in patients with PCOS is as effective as clomiphene citrate in inducing ovulation, and although the number of follicles produced by induction with letrozole were less than those produced by clomiphene, letrozole had a significantly greater effect on endometrial thickness than clomiphene citrate, and the incidence of pregnancy after intrauterine insemination was significantly higher, with a lower incidence of multiple pregnancy.

The infertility treatment related with polycystic ovary syndrome

The treatment of infertile women with polycystic ovary syndrome (PCOS) has not yet been established. Before any intervention is initiated, lifestyle modification with diet and exercise leading to weight loss should be emphasized in overweight women. The recommended first-line treatment for ovulation induction remains clomiphene citrate. If clomiphene citrate use fails to result in ovulation or pregnancy, the recommended second-line intervention is exogenous gonadotropins. The use of exogenous gonadotropins is related to an increased risk for multiple pregnancies, and, therefore, intense ovarian response monitoring is required. Laparoscopic ovarian surgery is an alternative to gonadotropin therapy because this surgery is as effective as gonadotropin in pregnancy rate or live birth rate. However, the surgery may require additional ovulation induction drug and should be performed by well-trained surgeon, its use solely to induce ovulation is unwarranted. Recommended third-line treatment is in vitro fertilization (IVF). IVF reduces the risk of multiple pregnancies by using single-embryo transfer in women with PCOS. The use of metformin alone as first-line infertility therapy or in combination with clomiphene is surrounded by controversies. Aromatase inhibitors appear to be as effective as clomiphene citrate for induction of ovulation, but the drug is currently not approved for treatment of infertility. Further studies should demonstrate the efficacy and long term safety.

Supplementation of clomiphene citrate cycles with Cimicifuga racemosa or ethinyl oestradiol – a randomized trial

The anti-oestrogenic activity of clomiphene citrate (CC) on the cervical mucous and endometrium may be the reason for the relatively low pregnancy rates in CC induction cycles. Various follicular-phase supplements have been tried to improve cycle outcome in these patients. This study compared follicular-phase supplementation with either phytoestrogen (PE) or ethinyl oestradiol (EE) in CC induction cycles for the treatment of unexplained infertility. A total of 134 patients were randomly allocated to each treatment group (67 each). The PE group needed significantly fewer days for adequate follicular maturation, had a thicker endometrium and higher oestradiol concentration at the time of human chorionic gonadotrophin injection (all P < 0.001). The PE group had higher luteal-phase serum progesterone compared with the EE group. No significant difference was found regarding clinical pregnancy rates (14.0% versus 21.1%, respectively). In conclusion, the cycle characteristics in unexplained infertility women treated with clomiphene citrate induction and timed intercourse improved after follicular-phase supplementation with PE compared with EE supplementation. Further studies are needed to confirm the mechanism beyond these effects.

Evaluation of the relationship between plasma concentrations of en- and zuclomiphene and induction of ovulation in anovulatory women being treated with clomiphene citrate

To investigate the relationship between the plasma concentrations of clomiphene citrate (CC) isomers zu- (Zu) and enclomiphene (En), and ovulation outcome. Prospective, cohort study. Reproductive medicine and fertility center in a university teaching hospital, United Kingdom. Forty-two women with World Health Organization type 2 infertility. The clinical and biochemical features of patients who were about to start CC for induction of ovulation were recorded. Plasma concentration of Zu and En were monitored at three points (days 2, 8, and 21) throughout the treatment cycle(s). Ovulation. Thirty-nine patients completed the study. Both En and Zu accumulated throughout treatment. Among the 36 responders, there was no statistically significant relationship between the clinical and biochemical characteristics of the patients, En or Zu concentrations, and the dose required to induce ovulation. Moreover, the Zu and En concentrations were not different in the three patients who failed to respond. The concentrations of En and Zu in plasma, on their own or in combination with other covariates (e.g., weight, body mass index, free androgen index), are not a predictor of the ovulation response to CC or of the dose requirement. Further studies are needed to explore the role of additional covariates, including the presence of active metabolites, and the balance of the effects of En and Zu.