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

Objective: Since not all women wish to conceive a child through aggressive treatment, we investigated the usefulness of modified repeated intracyclic clomiphene citrate (CC) therapy (repeated CC therapy) as a newly devised administration method. Methods: We evaluated the effects of CC administration on menstrual cycle length and retrospectively compared ovulation and pregnancy in 220 women who received CC at our hospital. Patients in the conventional method group received 50 mg per day for five days, starting on the fifth day of menstruation (withdrawal bleeding). Groups with and without menstrual cycle shortening after conventional CC administration were compared. The repeated CC therapy group was also compared with the non-shortened group. Repeated CC therapy was administered for the first five days as in the conventional method, and a second five-day repeat treatment was administered after an interval of five to seven days. Pregnancy rates, including indirect pregnancies, were evaluated by three different methods. Results: Ovulation and pregnancy rates were significantly better in the shortened group than in the non-shortened group (P < 0.001 and P = 0.010, respectively). Even in the non-shortened group, ovulation and pregnancy rates including indirect pregnancies were significantly improved when ovulation was observed with repeated CC therapy (P < 0.001 and P = 0.022, respectively). Conclusions: For patients whose menstrual cycle was not improved or shortened, repeated CC therapy as the newly devised CC administration method is useful as the next step after the conventional CC administration method.

Clomiphene Citrate Induces ROS-Mediated Apoptosis in Mammalian Oocytes

The clomiphene citrate (CC), a nonsteroidal triphenylethylene compound, is a first line of medicine used for the induction of ovulation in anovulatory women worldwide. In spite of high ovulation induction with the use of CC, the pregnancy rate is much lower. Such a discrepancy could be due to the peripheral anti-estrogenic effect of CC, particularly at the level of ovary, endometrium and cervical mucus. CC induces ovulation by binding to the estrogen receptors and generates hypoestrogrnic state in hypothalamus leading to release of pituitary gonadotropins. CC may have a direct effect at the level of ovary but the molecular mechanism remains unclear. Animal studies suggest that the CC induces apoptosis in granulosa cells and results hypoestrogenic state in the ovary. Reduced estradiol 17β level in the ovary affects development and maturation of oocyte leading to oocyte apoptosis. Further, CC increases hydrogen peroxide (H2O2) level and thereby bax protein expression and DNA fragmentation in cumulus-granulosa cells as well as in oocytes. The exogenous supplementation of either estradiol 17β or melatonin reduces H2O2 level in ovary, delays meiotic cell cycle progression in oocyte and protects oocyte apoptosis. Hence, supplementation of estradiol 17β or melatonin along with CC could be beneficial to protect granulosa cell as well as oocyte apoptosis and inhibit deterioration of oocyte quality. Thus, maintenance of oocyte quality may overcome the adverse effect caused due to CC treatment during infertility management.

Randomized controlled trial of Letrozole versus Clomiphene citrate for induction of ovulation in polycystic ovarian syndrome (PCOS): A Malaysian experience

Background: The purpose of this study was to compare the effectiveness of Letrozole versus Clomiphene citrate for ovulation induction in polycystic ovarian syndrome (PCOS) with infertility. Methods: This was a prospective randomized trial involving 150 women with PCOS attending the Infertility Clinic at three hospitals in Malaysia. During the initial visit, anthropometric measurements and baseline investigations were performed. Patients were randomized to 5.0 mg Letrozole daily (75 patients) or 100 mg Clomiphene citrate daily (75 patients) from the fifth until the ninth day of menstruation. Serial transvaginal scans were performed to see the dominant follicles, endometrial thickness and number of follicles. Transvaginal scans were performed serially to look for evidence of ovulation. Results: The subjects were homogenously distributed. The difference between Letrozole and Clomiphene citrate for ovulation rate was 59 (78.7%) versus 40 (53.3%). Patients taking Letrozole exhibited a mean endometrial thickness (ET) at mid cycle of menses (Day 11-D14) of9.2 mm(SD ± 2.3) versus8.4 mm(SD ± 2.2) for patients taking Clomiphene citrate, and these differences were statistically significant

Simultaneous Letrozole and Clomiphene Citrate versus Letrozole Alone in Clomiphene Citrate Resistant Polycystic Ovary Syndrome: A Randomised Controlled Trial

Background: Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility. The therapeutic strategies for clomiphene citrate (CC)- resistant patients include the addition of corticosteroids, extended duration of clomiphene, gonadotrophin therapy, laparoscopic ovarian drilling, in vitro fertilization or the use of aromatase inhibitors recently. Letrozole decreases estrogen levels in the body, so it releases the hypothalamus and/or pituitary gland from the negative feedback of estrogen. This increases levels of gonadotrophins, which stimulates follicular growth. Objectives: To evaluate the role of letrozole alone and simultaneous use of letrozole and clomiphene citrate (CC) for ovulation induction in patients with clomiphene citrate-resistant PCOS (CCR-PCOS). Patients and Methods: This open-label randomised controlled study was conducted in the Department of Obstetrics and Gynecology, Faculty of Medicine, Zagazig University, Egypt during the period from February 2018 to June 2019. The study included 60 CCR-PCOS patients who were randomly allocated by independent personnel into two arms: group A (letrozole alone) or B (letrozole + CC). In either group, monitoring the mean follicular diameter and endometrial thickness in the days 10, 12, and 14 of the cycle by transvaginal ultrasound and Measurement of serum Progesterone (ng/ml) 7 days after the expected time of ovulation. Results: We investigated various clinical and sonographic factors that may predict the outcome of the method of induction of ovulation in CCR-PCOS with no significant affection for the results. There was a non-significant difference between the studied groups regarding ovulation and pregnancy per cycle or per patient. Conclusion: Letrozole alone or simultaneous use of letrozole and CC offers a good second-line option for induction of ovulation in CCR-PCOS patients. However, the combination of CC and letrozole did not add any benefit over the use of letrozole alone regards ovulation rate, follicular volume, endometrial thickness, pregnancy rate and live birth rate.

A meta-analysis on the improvement of endometrial receptivity of PCOS by Bushen recipe combined with Clomiphene

Objective: To systematically evaluate the efficacy and safety of Bushen Recipe combined with clomiphene compared with clomiphene in improving endometrial receptivity of polycystic ovary syndrome. Methods: The time limit is from the establishment of the database to January 2, 2020. A randomized controlled trial was conducted to compare the effects of Bushen Recipe combined with clomiphene and clomiphene on the endometrial receptivity of polycystic ovary syndrome (PCOS). Meta analysis was performed with RevMan5.3 software. Results: A total of 13 RCTS were included, with a total of 797 PCOS patients. The results of this meta-analysis show: there were statistically significant differences in the improvement of endometrial thickness [WMD=1.62,95%CI(1.22, 2.01), P <0.00001], endometrial type[RR=1.51,95%CI(1.28, 1.78), P <0.00001], uterine artery pulse index(PI) [WMD=-0.18,95%CI(-0.27, -0.09) , P <0.0001], uterine artery resistance index(RI)[WMD=-0.08,95%CI(-0.11, -0.05) , P <0.00001], pregnancy rate [RR=2.18,95%CI(1.55, 3.05), P <0.00001], TCM syndrome score[WMD=-6.97,95%CI(-8.97, -4.97) , P <0.00001], effective rate [RR=1.25, 95%CI (1.13, 1.37), P < 0.00001]. Conclusion: Compared with clomiphene alone, Bushen Recipe combined with clomiphene can effectively increase the thickness of endometrium and improve the type of endometrium, promote the blood perfusion of endometrium, improve the pregnancy rate, improve the clinical symptoms, reduce the TCM syndrome score, improve the total efficiency of treatment, with high clinical application value.

Physicians’ Attitude toward the Use of Metformin Prior to Clomiphene Citrate in Infertile Women with PCOS in Saudi Arabia

The goal of this study is to assess the different approaches gynecologists take while treating women with PCOS related infertility. Methodology: This is a quantitative cross-sectional study that involves 46 specialists and consultants from all over the kingdom of Saudi Arabia. The sample size was calculated based on the number of consultants and specialists members in the Saudi Obstetrical & Gynecology society “SOGS”, we could not find any statistics on how many Ob/Gyne doctors we have in Saudi Arabia. The paper is approved by the Unit of Biomedical Ethics, King Abdulaziz University. The research team prepared an online survey of 13 questions, sent to all Consultants and Specialists in the “SOGS” during the year of 2016. The SPSS was used for the analysis. Conclusion: There is no significant difference between the different approaches of the first line of management. Comparing between Metformin and Clomiphene Citrate, Thirty Seven percent of participants preferred to start by a combination while 32% preferred to start with the former and 30.4% with the latter. Most of the doctors preferred to use Metformin for the Obese patients 76.1%, a lower percentage prefers to use it with Overweight patients 54.3%.

Bilateral Retinal Detachment Secondary to Clomiphene Citrate

Purpose: The purpose of this study is to assess the relationship between Clomifene citrate and retinal detachment in particular. Methods: a 42-year-old woman has developed bilateral retinal detachment after three courses of clomiphene citrate. A literature research for bilateral retinal detachment does not include this severe ophthalmologic complication. Conclusion: This is the first reported case of bilateral retinal detachment after treatment with clomiphene citrate. The caution is warranted in treating infertility patients with CC, and patient should be well informed of this side effect before prescribing this therapy by gynecologist.

Letrozole versus Gonadotropin in Unexplained Infertile Couples Failed to Conceive with Clomiphene Citrate

Background:?Unexplained infertility represents about 15% - 20% of infertile couples. Usually, these cases need assistance. Clomiphene citrate is the most used drug for this problem but sometimes pregnancy failed to achieve it, so other options for assistance are gonadotrophin or letrezole. The objective of our study was to compare the pregnancy rate for letrezole and gonadotropin inunexplained infertile women’s who failed to conceive with clomiphene citrate. Methods: This prospective quasi-randomized trial was carried out in cytogenetic unite at obstetrics and gynecology department, Zagazig University Hospital. 140 infertile females were included, induction of ovulation by letrozole for half of them and by gonadotrophin for the other half. Results: There was statistically highly significant decrease in duration of stimulation, E2 levels and endometrial thickness at day of HCG in letrezole group, no significant difference between two groups as regard number of follicles and pregnancy rate per cycle, while the cumulative pregnancy rate and the cost of stimulation are significantly higher in gonadotrophin group. Conclusion: In patient with unexplained infertility who failed to conceive with clomiphene citrate, gonadotrophins have a higher pregnancy rate than letrezole. However, pregnancy rate was high enough with lower cost with letrezole to be acceptable and justified its use in this group of patients.

The advantage of low-dose clomiphene citrate for overweight women with anovulation

Background:To investigate the potential advantage of using low-dose clomiphene citrate to promote ovulation in women with overweight or obesity.Methods:The patients with overweight were divided randomly into regular clomiphene citrate group(clomiphene citrate 50 mg/d,n=83)and low-dose clomiphene citrate group(clomiphene citrate 25 mg/d,n=105).All patients received treatment from the 5th day of their menstrual cycles.Results:Luteinizing hormone levels and estradiol levels were more increased in the low-dose group compared with the regular group(P<0.05).Low-dose group showed significantly thicker endometrium,fewer dosage and shorter days of human menopausal gonadotropin,less numbers of mature follicles and lower rates of cancellation(P<0.05)on human chorionic gonadotropin day.After human chorionic gonadotropin injection,the ovulation rate in the low-dose group was significantly higher than the regular group(P<0.05).No difference was detected in the biochemical pregnancy rates both groups(P>0.05).Conclusion:The low-dose clomiphene citrate treatment significantly reduced the number of mature follicles and increased the thickness of endometrium on the human chorionic gonadotropin day with less side effects.The low-dose clomiphene citrate also achieved the better ovulation rate.

Effects of acupoint embedding combined with clomiphene in patients with polycystic ovary syndrome： a randomized controlled trial

Objective： To compare the efficacy of acupoint embedding combined with clomiphene with clomiphene alone in the treatment of patients with polycystic ovary syndrome （PCOS）. Methods： Sixty patients who met the diagnostic criteria of PCOS were randomly divided into the acupuncture-medicine combination （30 cases） and the single medicine （30 cases） groups. For a total of 4 menstrual cycles, patients in the acupuncture-medicine combination group were treated with acupoint embedding combined with oral clomiphene, whereas those in the single medicine group were treated with clomiphene only. Clinical efficacy of the two treatments was observed after 2 months of treatment, and body mass index （BMI）, number of menstrual cycles, luteinizing hormone （LH）, follicle stimulating hormone （FSH）, LH / FSH ratio, and serological levels of testosterone before and after treatment were analyzed. Results： Compared with the single medicine group, patients in the acupuncture-medicine group showed lower BMI （24.3 ± 1.6 vs 26.1 ± 1.8） and higher number of menstrual cycles （3.6 ± 1.5 vs 2.8 ± 1.2）; the differences were statistically significant （P = 0.018, P = 0.025）. LH （9.53 ± 5.46 vs 12.29 ± 5.67） and LH / FSH （1.02 ± 0.57 vs 1.45 ± 0.23） levels were significantly decreased （P = 0.041, P = 0.039）. Compared to before treatment, BMI （24.3 ± 1.6 vs 27.6 ± 1.4） was lower and the number of menstrual cycles was higher （3.6 ± 1.5 vs 1.8 ± 0.8） after treatment; the differences were statistically significant （P = 0.034, P = 0.024）. The levels of LH （9.53 ± 5.46 vs 18.12 ± 11.04） and LH / FSH （1.02 ± 0.57 vs 2.38 ± 1.09） were significantly decreased （P = 0.007 P = 0.005）. Total effective rates were 76.67% and 70% in the acupuncture-medicine combination and single medicine groups, respectively; the difference between the two groups was statistically significant （P = 0.043）. Conclusion： Acupoint embedding combined with clomiphene in the treatment of PCOS could downregulate BMI, LH, and LH / FSH ratio, and increase the number of menstrual cycles.

Effect of metformin combined with clomiphene on insulin resistance, oxidative stress response and T cell immune response in patients with PCOS

Objective: To study the effect of metformin combined with clomiphene on insulin resistance, oxidative stress response and T cell immune response in patients with polycystic ovarian syndrome (PCOS). Methods: A total of 94 patients who were diagnosed with PCOS in Jingzhou Second People's Hospital between September 2014 and October 2016 were selected and randomly divided into the combined group who received the metformin combined with clomiphene therapy and the control group who received clomiphene therapy. The insulin resistance, oxidative stress response and T cell immune response were evaluated before treatment and 3 menstrual cycles after treatment. Results: 3 menstrual cycles after treatment, HOMA-IR level, serum F-Ins, F-CP, TOS, MDA, AOPP and IL-17 contents as well as peripheral blood RORγt mRNA expression of combined group were significantly lower than those before treatment while HOMA-β level, serum TAS, SOD, GSH-Px, VitC, VitE, IL-10 and TGF-β1 contents as well as peripheral blood Foxp3 mRNA expression were significantly higher than those before treatment;HOMA-IR and HOMA-β levels, serum F-Ins, F-CP, TOS, MDA, AOPP, IL-17, TAS, SOD, GSH-Px, VitC, VitE, IL-10 and TGF-β1 contents as well as peripheral blood Foxp3 and RORγt mRNA expression of control group were not different from those before treatment. Conclusion: Metformin combined with clomiphene can significantly improve the insulin resistance, oxidative stress response and T cell immune response in patients with PCOS.

Acupuncture-induced improvement of endometrial receptivity of rats with polycystic ovary syndrome treated by Clomiphene for ovarian stimulation

Objective To observe acupuncture effects on endometrial receptivity of the rats with polycystic ovary syndrome （PCOS） treated by ovarian stimulation with Clomiphene to explore its mechanisms. Methods eGOS rat model was experimentally induced by subcutaneous injection of oil solution of dehydroepiandrosterone （DHEA） in immature （24-day-old） female rats for continuous 20 days. The same dose of oil was given for an equivalent length of time to animals in a control group （Group Con）. The rats with PCOS were randomly divided into a model group （group M）, a Clomiphene treatment group （group C）, a Clomiphene plus acupuncture group （group C＋ A）. The treatments were given for 5 days since 80 days after birth. Half of the rats were killed by decapitation after treatment finished, and the serum, uteri and endometria were obtained. The other half mated with male rats, and they were killed at the 8th day of pregnancy. We observed the implantation number and condition of pregnant uteri. Results Compared with group C, the animals in group C＋A had higher implantation rate and more average implanted embryos （P〈0. 01 ）, higher serum estradiol （E2） level （P〈0.01 ）, better development of endometrium, and increased mRNA and protein expressions of molecular markers of endometrial receptivity （P〈0.01）, which were closer to those in the control group. Conclusion Acupuncture could improve poor endometrial receptivity of PCOS rats with ovarian stimulation by citrated Clomiphene and promote implantation. The effects may be related with its up-regulation of serum E2 level, mRNA and protein expressions of molecular markers of endometrial receptivity.

Study of Combined Use of Clomiphene Citrate and Gonadotropins on the Infertile Patients with PCOS

Objective To investigate the efficacy and safety of combined use of clomiphene citrate （CC） and gonadotropins （Gn） on the infertile patients with PCOS. Methods A total of 367 infertile patients with PCOS were included in this retrospective study. Patients received CC from menstrual cycle day 3 until the day of triggering and human menopausal gonadotrophins （hMG） from menstrual cycle day 5 until the ovulation day. Gn duration and doses, serum LH and estradiol levels, transferable embryos, incidence of OHSS, frozen-thawed embryo implantation and clinical pregnancy rates were compared among CC plus hMG, long and short protocols. Results Gn duration and doses, blood estrogen level transferable embryos and incidence of OHSS in the group of CC plus hMG were decreased significantly than those of long and short protocols. No differences were observed in the frozen-thawed embryo implantation and clinical pregnancy rates among three groups. Conclusion Mild stimulation of CC combined with hMG on infertile patients with high risk for OHSS is safe and efficient.

Clomiphene Citrate as An Adjuvant to hMG Stimulation of the Ovaries in Mid-to-late Follicular Phase and Subsequently Pregnancy Outcome of Frozen-thawed Embryo Transfers

Objective To compare the results of a novel regimen of human menopausal gonadotrophin （hMG） in combination with clomiphene citrate （CC） in mid-to-late follicular phase with those of a short protocol of GnRH agonist （GnRHa） and hMG used for IVF. Methods In the retrospective study, 842 patients undergoing IVF were collected and classified into two groups： hMG in combination with CC in mid-to-late follicular phase （group A, n=319） and short protocol of GnRHa-hMG （group B, n=523）. The main outcome measures were ovarian responses in stimulation cycles and pregnancy outcomes in subsequent frozen-thawed embryo transfer （FET） cycles. Results In group A, the serum LH concentration on day 8 -10 was similar with that on the day of hCG administration （2.43 ± 1.92 IU vs 2.51 ±2.05 IU）. The number of mature follicles and oocytes retrieved was significantly lower in group A than in group B while the fertilization rate and the cleavage rate were comparable. The clinical pregnancy rate （47. 79% vs 48.04%）, the implantation rate （32.49% vs 33.11%） and the cumulative pregnancy rate （58.09% vs 60.22%） were respectively similar in group A and group B. Conclusion hMG in combination with CC in mid-to-late follicular phase results in the same pregnancy outcome as short protocol. The novel protocol may take the advantage of eliminating the occurrehce of a premature endogenous LH Surge.

Clomiphene Citrate or Medroxyprogesterone Acetate with Human Menopausal Gonadotropin in Poor Responders during In vitro Fertilization/Intracytoplasmic Sperm Injection Treatments Combined with Embryo Cryopreservation?

Objective:This study aimed to compare the efficacy of clomiphene citrate(CC)with human menopausal gonadotropin(hMG)and that of medroxyprogesterone acetate(MPA)with hMG in poor responders defined according to the Bologna criteria.Methods:The data of patients with poor ovarian response(POR)according to the Bologna criteria from September 2016 to November 2017 were retrospectively reviewed.All participants received either CC+hMG or the progesterone-primed ovarian stimulation protocol(PPOS)protocol.Results:A total of 340 patients and 563 in vitro fertilization cycles were analyzed in this study.The incidence of spontaneous luteinizing hormone(LH)surge and the mean LH level on trigger day were significantly lower in the PPOS group than in the CC+HMG group(0.04%vs.3.49%and 4.26±3.59 vs.9.38±6.92 mIU/mL,respectively,P<0.05);however,the incidence of premature ovulation was similar between the two groups.The number of viable embryos harvested was not statistically different between the two groups(1.7±1.1 vs.1.5±0.8,P=0.06).The mean dose and duration of hMG were significantly higher in the PPOS group than in the CC+hMG group(908.7±556.6 vs.177.9±214.5 IU and 6.0±3.4 vs.1.2±1.5 days,respectively,P<0.05).However,the number of oocytes retrieved,number of metaphase II oocytes,and fertilization rate were comparable between the two groups.Conclusions:The CC with low-dose gonadotropin strategy was superior to the MPA with hMG protocol for POR.

Association of anti-mullerian hormone and free androgen index level on response to clomiphene citrate in PCOS infertile women

Background:Polycystic ovary syndrome(PCOS)is the leading cause of anovulatory infertility.Clomiphene citrate,insulin-sensitizing drugs,aromatase inhibitors,gonadotropins,or laparoscopic ovarian drilling are various methods used for ovulation induction in women with PCOS.PCOS women with high levels of anti-mullerian hormone(AMH)and free androgen index(FAI)do not respond well to ovulation induction.This prospective observational study explores the relationship between FAI and AMH levels on ovarian response to clomiphene citrate in infertile women with PCOS.Methods:This prospective observational study included 40 infertile with PCOS who underwent ovulation induction with clomiphene citrate with dose ranging from 50 to 150 mg.Participants were classified into four phenotypes by NIH(National Institute of Health)consensus panel criteria.The clinical and endocrine parameters of participants who were sensitive to clomiphene were compared to those who were resistant.Results:The most common phenotype was A,with all three features of PCOS:hyperandrogenism,ovulatory dysfunction,and polycystic ovarian morphology.There was no significant difference in clinical and endocrine parameters among the different phenotypes of PCOS except AMH and FAI values.The mean FAI was 9.39
1.11 and AMH 7.26
0.48(ng/ml)in clomiphene resistant and 5.31
1.93 and 3.69
1.84(ng/ml)respectively in clomiphene-sensitive women.Women with FAI>7.5 and AMH>7 ng/ml might be resistant to clomiphene.Conclusion:FAI and AMH values were significantly higher in women resistant to clomiphene induction.AMH and FAI may help women with PCOS to tailor their ovulation induction protocol.

Induction of Ovulation with Clomiphene Citrate Combined with Bromocriptine in Polycystic Ovary Syndrome Patients with Infertility: A Prospective, Randomized, and Controlled Clinical Trial

Background:To investigate the therapeutic effects of bromocriptine(BCT)combined with clomiphene citrate(CC)in the induction of ovulation in polycystic ovary syndrome(PCOS)patients with infertility.Methods:A prospective,randomized,and controlled clinical trial was performed on 100 PCOS patients with infertility.Patients were randomly divided into two groups(n=50),patients in control group were treated with 50 mg CC from day 3 to day 7 of the menstrual cycle,and those in observation group(CC+BCT)were given 50 mg of CC from day 3 to day 7 of the menstrual cycle along with 2.5 mg of BCT daily for the full cycle.Patients in both groups were treated for one cycle.Blood was extracted from patients on day 3 of the menstrual cycle,the day of human chorionic gonadotrophin(hCG)injection,and day 7 after hCG injection to measure serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),prolactin(PRL),estradiol(E_(2)),total testosterone(T)and progestin(P).Vaginal ultrasound was used to determine the thickness of endometrium and follicle size and count.Results:There was no significant difference in basal hormone levels between two groups.The success rate of ovulation induction in control group and observation group was 72.0%and 75.4%,respectively,no significant difference was found between two groups(P>0.05).The ongoing pregnancy rate(18.4%)in observation group was significantly higher than that in control group(8.0%).On the day of hCG injection,no significant differences in the levels of FSH,E_(2),and P were found between two groups,while LH was lower,and levels of PRL and T were significantly lower in observation group than those in control group(all P=0.00).On day 7 after hCG injection,no significant differences in the levels of E_(2) and P were found between two groups,while PRL level was significantly lower in observation group than that in control group,and the endometrial thickness in observation group(10.20±1.92 mm)was significantly higher than that in control group(9.22±1.88 mm)(P=0.01).Conclusions:Compared with the use of CC alone,BCT combined with CC can increase the success rate of ovulation induction-assisted pregnancy in PCOS patients,decrease the levels of PRL,LH,and T and increase the endometrial thickness in implantation window.Those data suggest that dopamine agonist BCT may reduce the pituitary hormone and androgen levels,reduce endometrial vascular resistance,and increase endometrial blood supply to improve the infertility outcomes of PCOS patients with infertility.

Effects of the Interval between Ovulation Induction using Clomiphene Citrate and Frozen Embryo Transfer on Pregnancy Outcome

Objective:To explore the best timing for frozen embryo transfer(FET)after ovarian stimulation and egg retrieval using the clomiphene citrate(CC)+human menopausal gonadotropin(hMG)ovulation induction regimen through a retrospective analysis.Methods:Data of patients who underwent CC+hMG ovulation induction and FET from January 2014 to December 2019 were analyzed retrospectively.The patients were divided into three groups according to the interval from egg retrieval to FET:CC1(within 1 menstrual cycle),CC2(2 menstrual cycles),and CC3(≥3 menstrual cycles).Indicators such as hormone levels and pregnancy outcomes were recorded to explore the effect of different intervals on pregnancy outcome.Results:A total of 1,082 transfer cycles were included in this retrospective analysis.The implantation,clinical pregnancy,and live birth rates in the CC1 group were significantly lower than those in the CC2 and CC3 groups(P<0.05).The E2/P4 ratio on progesterone injection day(3 days before thawed embryo transfer)was lower in the CC1 group than in the other groups(P<0.05).After adjusting for all factors using multifactor regression analysis,the interval between egg retrieval and FET was found to be an independent predictor of the implantation,pregnancy,and live birth rates.Conclusion:An interval of more than one menstrual cycle between the day of egg retrieval after ovarian stimulation with the CC+hMG ovulation induction regimen and the day of FET can result in high implantation,clinical pregnancy,and live birth rates,which can lead to an improved pregnancy outcome.

A novel herbal combination ameliorates ovarian dysfunction and regulates altered biochemical parameters in rats with letrozole-induced polycystic ovary syndrome

Objective:To investigate the potential activity of novel herbal combination and novel herbal formulation(syrup)in female Sprague Dawley rats with letrozole-induced polycystic ovary syndrome(PCOS).Methods:Forty-two rats were randomly divided into seven groups with six rats in each group.Group 1 received 0.5%carboxy methylcellulose orally for 37 days and served as the normal control group.Group 2 was orally administered with letrozole of 1 mg/kg for 21 days and served as the PCOS induction group without treatment.Group 3 to 7 were administered with letrozole of 1 mg/kg for 21 days orally to induce PCOS,and then respectively received clomiphene citrate at 1 mg/kg,100 and 200 mg/kg of novel herbal combination,200 mg/kg of novel herbal formulation(syrup),and 400 mg/kg of marketed formulation of Pushyanuga churna,once daily for 15 days.Effects of the novel herbal combination and its syrup formulation were evaluated on the hormonal profile,the levels of antioxidants,the lipid profile and on the ovarian morphology,using letrozole-induced PCOS model in rats.Results:Letrozole caused alterations in hormonal levels and lipid levels similar to PCOS and ovarian histology showed presence of ovarian cysts confirming the induction of PCOS in rats.On treatment with the novel herbal combination and its syrup formulation in PCOS-induced rats,the altered hormonal and lipid profiles showed significant recovery to normal levels.Ovarian histology confirmed the restoration of folliculogenesis in the PCOS-induced rats.The treatment with the syrup formulation of novel herbal combination was found to be more effective than novel herbal combination and showed better recovery in various parameters evaluated.The results of the study,however,suggested that treatment with novel herbal combination and its syrup formulation provided minimal protection against oxidative stress caused due to the induction of PCOS.Conclusions:The integrated approach for management of PCOS is to counterbalance the limitations associated with modern therapy.Both the novel herbal combination and the syrup formulation of novel herbal combination show efficacy in the management of PCOS in rats and restore folliculogenesis in the ovary.The syrup formulation of novel herbal combination is most effective in the management of PCOS and shows potential to be developed as an adjuvant therapeutic agent.

Treatment of hypogonadotropic male hypogonadism: Case-based scenarios

The aim of this study is to review four case-based scenarios regarding the treatment of symptomatic hypogonadism in men. The article is designed as a review of published literature. We conducted a PubMed literature search for the time period of 1989-2014, concentrating on 26 studies investigating the effcacy of various therapeutic options on semen analysis, pregnancy outcomes, time to recovery of spermatogenesis, as well as serum and intratesticular testosterone levels. Our results demonstrated thatexogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis. Cessation of exogenous testosterone should be recommended for men desiring to maintain their fertility. Therapies that protect the testis involve human chorionic gonadotropin （hCG） therapy or selective estrogen receptor modulators （SERMs）, but may also include low dose hCG with exogenous testosterone. Off-label use of SERMs, such as clomiphene citrate, are effective for maintaining testosterone production long-term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. We concluded that exogenous testosterone supplementation decreases sperm production. It was determined that clomiphene citrate is a safe and effective therapy for men who desire to maintain fertility. Although less frequently used in the general population, hCG therapy with or without testosterone supplementation represents an alternative treatment.