Effect of Clomiphene Citrate on the Ultrastructure of Testis in Albino Rats

SUMMARY: The aim of the present work was to study the closer effect of clomiphene citrate on the ultrastructure of the testis of adult albino rats to provide a basis for optimizing this drug in the treatment of male infertility. The testes were removed from both groups under anesthesia and then prepared for examination by light using hematoxylin and eosin stains and a transmission electron microscope. Semithin sections were cut into 1 µm thick sections, stained with toluidine blue, and examined by light microscopy for a survey. The desired areas were placed in the center, and other areas were trimmed. Primary spermatocytes showed marked nuclear changes (pyknosis), and their nuclear membranes were ill-defined and disrupted. The cytoplasm showed widespread degeneration of mitochondria and lysosomes and focal degeneration of the rough endoplasmic reticulum compared with the control group. The spermatids were pale, and the two phases of spermatogenesis were distinctly identifiable in the control group but were confused in the treated group. Some spermatids had interrupted nuclear membranes, also containing degenerated mitochondria, focal fragmentation of rough endoplasmic reticulum, and free ribosomes. Spermatozoa in the treated group appeared deformed compared to the control, where they had deformed head caps. Leydig cells of the treated group have an irregularly shaped nucleus, with focal chromatin aggregation and peripheral chromatin condensation on the inner surface of the nuclear membrane. The observations of the present work indicate a possible causal relationship between testicular affection and ingestion of clomiphene citrate, which can be avoided by close medical observations using ultrasonography, semen analysis, or testicular biopsy to detect early malignant changes. Furthermore, the drug should not be used for more than three to six cycles and should be stopped for at least three cycles before reuse. When clomiphene citrate is ineffective in the treatment of male infertility, human menopausal gonadotropin (hMG) administration is typically selected. However, high-dose hMG therapy is associated with a variety of adverse effects. In this work, we report the success of a modified clomiphene citrate regimen in increasing sperm count without any hazards to the testicular tissue.

El objetivo del trabajo fue estudiar el efecto del citrato de clomifeno sobre la estructura de los testículos de la rata albina adulta, con la finalidad de determinar la mejor manera de utilizar este fármaco en el tratamiento de la infertilidad masculina. Los testículos se extrajeron bajo anestesia y para su análisis a través de microscopio de luz se tiñeron con HE. Además, las muestras fueron preparadas para su examen con microscopía electrónica de transmisión. Por otra parte, se cortaron secciones semifinas de 1 µm de espesor, se tiñeron con azul de toluidina y se examinaron mediante microscopía óptica. Los espermatocitos primarios mostraron cambios nucleares marcados (picnosis) y sus membranas nucleares estaban mal definidas y alteradas. En el grupo experimental las células presentaban el citoplasma con degeneración generalizada de las mitocondrias y de los lisosomas y una degeneración focal del retículo endoplásmico rugoso en comparación con el grupo control. Las espermátidas estaban pálidas y las dos fases de la espermatogénesis eran claramente identificables en el grupo control, pero se confundían en el grupo tratado. Algunas espermátidas tenían membranas nucleares interrumpidas, y también contenían mitocondrias degeneradas, fragmentación focal del retículo endoplásmico rugoso y ribosomas libres. Los espermatozoides del grupo tratado se presentaban deformados en comparación con el control. Las células de Leydig del grupo tratado presentaban un núcleo de forma irregular, con agregación focal de cromatina y condensación de cromatina periférica en la superficie interna de la membrana nuclear. Las observaciones del presente trabajo indican una posible relación causal entre la afección testicular y la ingestión de citrato de clomifeno, que puede evitarse mediante observaciones médicas minuciosas a través de ecografía, análisis de semen o biopsia testicular para detectar cambios malignos tempranos. Además, el medicamento no debiera ser usado durante más de tres a seis ciclos y debe suspenderse durante al menos tres ciclos antes de volver a usarlo. Cuando el citrato de clomifeno es ineficaz en el tratamiento de la infertilidad masculina, normalmente se selecciona la administración de gonadotropina menopáusica humana (hMG). Sin embargo, la terapia con hMG en dosis altas se asocia con una variedad de efectos adversos. En este trabajo, informamos el éxito de un régimen modificado con citrato de clomifeno para aumentar el recuento de espermatozoides sin riesgo para el tejido testicular.

Treatment of Infertility in Women with Polycystic Ovary Syndrome in a Single Center Study

Background: Anovulatory infertility is caused by polycystic ovarian syndrome in 80 percent of patients. Preconception guidelines, such as lifestyle modification (weight loss) to avoid fetal neural tube abnormalities, and quitting smoking and drinking alcohol, are all part of the early treatment. A clomiphene citrate medication for timed intercourse is the first-line pharmacological treatment for producing ovulation. Exogenous gonadotropins or laparoscopic ovarian surgery are two options for second-line pharmaceutical treatment (ovarian drilling). Ovulation induction using clomiphene citrate or gonadotropins is effective, with a 70 % cumulative live birth rate. When laparoscopy is necessary, ovarian drilling should be done; this operation is usually successful in around half of the instances. Finally, when the previous interventions have failed, a high-complexity reproduction treatment (in vitro fertilization or intracytoplasmic sperm injection) is recommended. There is no evidence that metformin should be used routinely in the treatment of infertility in anovulatory women with polycystic ovary syndrome. Aromatase inhibitors show promise, but more research is needed to confirm their safety.Methods:This study was conducted in Department of gynecology and obstetrics, Dhaka Medical College Hospital, Dhaka, from January 2019 to December 2019. A total number of 100 patients with multiple myeloma were analyzed cytogenetically by interphase fluorescence in situ hybridization (iFISH). The collected data were analyzed by using the Statistical Package for Social Science (SPSS-24) for windows version 24.0.Conclusion:PCOS is a frequent syndrome and the most frequent cause of infertility. PCOS is defined as a syndrome with at least two of three of the Rotterdam criteria. A complete evaluation of the infertility is needed to exclude other causes of infertility..

Efeitos do citrato de clomifeno, letrozol e estradiol sobre apoptose em células do cumulus oophorus humano / Effects of clomiphene citrate, letrozole and estradiol on apoptosis in human cumulus oophorus cells

Citrato de clomifeno (CC) e letrozol (LE) são indutores de ovulação que, apesar das altas taxas de ovulação confirmada, atingem baixas taxas de gravidez. Este estudo teve como objetivo investigar os efeitos de CC e LE in vitro, isoladamente ou em combinação com estradiol (E), na apoptose de células do cumulus oophorus humano. Realizamos um estudo prospectivo controlado utilizando culturas primárias de células do cumulus de pacientes submetidas à fertilização in vitro (n=22). A coloração com Giemsa e a imunocitoquímica para alfa-inibina foram utilizadas para avaliar a pureza e a morfologia da cultura celular. A viabilidade celular foi avaliada pelo ensaio MTT, o ciclo celular por citometria de fluxo e a expressão gênica de Caspase-3, Bax e Superóxido dismutase 2 (SOD-2) e S26 por reação em cadeia de polimerase (PCR) em tempo real. As células foram tratadas por 24 horas em 5 grupos de tratamento: CC, CC + E, LE, LE + E e controle. Nenhum dos tratamentos afetou a viabilidade celular, mas o LE reduziu a porcentagem média de células na fase S em relação ao controle (24,79 versus 21,70, p=0,0014). O tratamento com CC aumentou a expressão gênica de Bax (4 vezes) e SOD-2 (2 vezes), que foi revertida quando adicionado E à cultura. A expressão de SOD-2 aumentou em células tratadas com LE quando comparado ao controle (4 vezes), que foi também revertida por adição de E. Estes achados sugerem que CC e LE não afetam significativamente a viabilidade das células do cumulus humana. Porém, houve modulação na expressão de genes envolvidos na apoptose por essas drogas isoladamente e em associação com E, sugerindo que CC e LE podem ter efeitos diretos nas células do cumulus além de seus mecanismos de ação conhecidos.

Clomiphene citrate (CC) and letrozole (LE) are ovulatory stimulants that, despite high ovulation rates, achieve low pregnancy rates. This study aimed to investigate the in vitro effects of CC and LE, alone or in combination with estradiol (E), on apoptosis in human cumulus cells. We performed a controlled prospective study using primary cumulus cell cultures from patients undergoing in vitro fertilization (n=22). Giemsa stain and alpha-inhibin immunocytochemistry was used to assess cell culture purity and morphology. Cell viability was evaluated by MTT assay, cell cycle status by flow cytometry, and Caspase-3, Bax and superoxide dismutase 2 (SOD-2), and S26 gene expression by real-time polymerase chain reaction (qPCR). Cells were treated for 24 hours in 5 conditioned media: CC, CC + E, LE, LE + E and control. None of the treatments affected cell viability, but LE reduced the mean percentage of cells in the S phase compared to control (24.79 versus 21.70, p=0.0014). CC treatment increased mRNA expression of Bax (4 fold) and SOD-2 (2 fold), which was reversed by co-treatment with E. SOD-2 expression increased in cells treated with LE compared to control (4 fold), which was also reversed by E. These findings suggest that CC and LE do not significantly affect the viability of human cumulus cells. Still, the expression of genes involved in apoptosis was modulated by these drugs alone and in association with E, suggesting that CC and LE may have direct effects on cumulus cells beyond their known mechanisms of action.

Atualizações na terapêutica farmacológica para infertilidade na mulher diagnosticada com síndrome de ovários policísticos: revisão de literatura / Updates on pharmacological treatments for infertility in women diagnosed with polycystic ovary syndrome: a literature review

Objetivo: Abordar atualizações referentes à terapia medicamentosa para indução da ovulação nas mulheres diagnosticadas com síndrome dos ovários policísticos (SOP). Métodos: Revisão de literatura por meio de levantamento bibliográfico do período de 1975 a 2021, nas bases eletrônicas PubMed, SciELO e MedLine, complementado pela Diretriz Internacional Baseada em Evidências para a Avaliação e Manejo da SOP de 2018 e pelo manual da Febrasgo para SOP. Sete descritores que atendessem à finalidade da pesquisa foram utilizados. Resultados: A literatura aponta atualmente algumas drogas como opção na terapêutica para a indução de ovulação, como metformina, letrozol e citrato de clomifeno, evidenciando que o uso de letrozol isolado e em associação com a metformina apresentaram melhores taxas de ovulação, 71,5% e 75,4%, respectivamente. Conclusão: O uso do letrozol isolado ou combinado com a metformina apresentou os melhores resultados nas taxas de gravidez e ovulação, todavia o tratamento para indução ovulatória deve ser individualizado.(AU)

Objective: To address updates of medicinal therapy for ovulation induction in women diagnosed with polycystic ovary syndrome (PCOS). Methods: Reviewing Literature through a bibliographic survey from 1975 to 2021, on the electronic databases PubMed, SciELO and MedLine, complemented by the International Evidence-Based Guideline for the Evaluation and Management of PCOS 2018 and the Febrasgo guide for PCOS. Seven descriptors that matched to the purpose of the research were applied. Results: Some drugs are currently indicated in the literature as an option for ovulation induction therapy, such as: metformin, letrozole and clomiphene citrate, showing that the use of letrozole alone and in association with metformin had better ovulation rates, 71.5% and 75.4%, respectively. Conclusion: The use of letrozole alone or combined with metformin showed the best results in pregnancy and ovulation rates, however, treatment for ovulatory induction must be individualized.(AU)

Clomiphene versus letrozole: a better agent for ovulation induction

Background: Anovulatory dysfunction is a commonly encountered problem which is responsible for about 40% of female infertility. One of the leading causes of female infertility is polycystic ovarian syndrome (PCOS). Clomiphene citrate has been the drug of choice in treating women with anovulatory infertility. However, in recent years, letrozole, an aromatase inhibitor, has emerged as alternative ovulation induction agent. Aim of this study was to compare efficacy of clomiphene citrate and letrozole as first line therapy for ovulation induction in polycystic ovarian syndrome.Methods: This study was a hospital based prospective comparative study done in MVJ MC and RH involving 100 females suffering from infertility due to anovulation. They were divided into 2 groups of 50 each. One group was given clomiphene citrate 50 mg while another group was given letrozole 2.5 mg from day 3 to day 7 of menstrual cycle. Ultrasonographic follicular monitoring was done and injection beta HCG 5000 IU was given once follicle reached optimum size (≥18 mm) and endometrial thickness was adequate (≥7 mm). Patients were advised for timed intercourse after 24-36 hours of HCG administration. Ovulation was detected by sonographic findings of follicular rupture done after 48 hours. Primary outcomes measured were number of growing follicles (≥18 mm), endometrial thickness, ovulation rate and pregnancy rate.Results: In our study there was significant difference in the outcomes of ovulation induction between letrozole group and clomiphene group.  Women who received letrozole showed improved endometrial growth (8.44 mm versus 7.86 mm), ovulation rate (72% versus 56%) and pregnancy rate (22.2% versus 14.3%) than those who received clomiphene. However, variation in follicular growth was negligible between the two groups (1.28 versus 1.36).Conclusions: Letrozole is a superior alternative to clomiphene citrate for ovulation induction in cases of PCOS with anovulatory menstrual cycle, and can be considered as first-line therapy for ovulation induction in such women.

Study of hundred cases of infertility in polycystic ovarian syndrome and its management outcome

Background: Polycystic ovarian syndrome (PCOS) is relatively common endocrine disorder in reproductive aged women, which leads to reproductive, metabolic and endocrine abnormality. About 70 to 80% patients with PCOS have complained of infertility due to anovulation. Due to advanced diagnostic facility by endoscopic evaluation in infertility, incidence of PCOS has increased now a days.Methods: This is study of 100 cases of infertility with polycystic ovarian syndrome and its pregnancy outcome. In this study, from May 2019 to April 2020, 100 cases of infertility with PCOS were studied at tertiary care hospital. Hormonal assay, ultrasound and laparoscopy were used as diagnostic technique. Clomiphene citrate, letrozole, metformin, and laparoscopic ovarian drilling were used as treatment modalities.Results: The maximum number of patients in the study group are seen in the age group of 21-25 years. Menstrual irregularities are the most common presenting symptom affecting 70% females. Primary infertility is most commonly associated with PCOS. In PCOS, there is increased LH:FSH ratio. On USG examination, there are enlarged ovaries in 82% cases.Conclusions: PCOS is an emerging disease of new generation with high prevalence in infertile women. After proper diagnosis, management with lifestyle modification, pharmacotherapy with clomiphene citrate, letrozole and metformin are used as per necessities. Operative laparoscopy with ovarian drilling is the main treatment which results in good conception rate.

Comparison of pregnancy outcome between clomiphene citrate and sequential clomiphene citrate+human menopausal gonadotropin in intrauterine insemination

Background: Intrauterine insemination (IUI) has been widely used as a common treatment for infertile couples. This study compares the sequential clomiphene citrate (CC) treatment with CC and human menopausal gonadotropin (hMG) treatment in women undergoing IUI. Therefore, this study was designed to determine the effects of addition of gonadotropin (CC+hMG) would improve the pregnancy rate in women undergoing IUI. And also compare the sequential CC+hMG treatment with CC treatment in women undergoing IUI. Methods: A cross-sectional study design was conducted at D. Y. Patil Fertility Centre, D.Y Patil Hospital, Navi Mumbai from September 2018 to August 2019. Source populations were all patients who live in Mumbai, Maharashtra, India. A total of 67 patients were enrolled in this study. (It consisted of 67 sub fertile couples undergoing ovarian stimulation for IUI cycles). Results: There was no significant difference between the two studied groups regarding endometrial thickness (8.3±2.1 versus 9.7±2.8, respectively), number of mature follicles on the day of hCG injection (3.3±1.2 versus 3.5±1.1, respectively) and, but there was significant difference between the CC+hMG group and CC group regarding the total dose of gonadotropins used in ovulation induction (305±23.8 versus 655±192; total IU, respectively) p<0.05. Conclusions: Women undergoing IUI, ovarian stimulation CC combined with hMG, significantly improved the pregnancy and live birth rates as compared to that of CC group. In women undergoing ovarian stimulation and IUI, there are no significant differences in pregnancy and live birth rates among the various stimulation protocols.

Lomiphene citrate versus letrozole as first line ovulation induction drug in infertile anovulatory polycystic ovarian syndrome women: a prospective randomized controlled trial

Background: The present study was design to compare letrozole (5 mg) and clomiphene citrate (100 mg) as first line ovulation induction drug in infertile anovulatory polycystic ovarian syndrome (PCOS) women.Methods: This prospective randomized clinical trial included 60 cases of PCOS with anovulatory infertility. The first group comprised of 30 patients who received 5 mg letrozole daily and the second group received 100 mg clomiphene citrate daily for 5 days starting on day 2-5 of menses. Both the groups were followed by ultrasound for follicle monitoring, ovulation and endometrial thickness. When dominant follicle reaches a diameter of more than or equal to 18mm and endometrial thickness ≥7.5 mm, human chorionic gonadotrophin (hCG) 5,000 IU was given intramuscularly and timed intercourse was advised. Main outcome measures were occurrence of ovulation, endometrial thickness and pregnancy rates.Results: The mean age, body mass index, and number of cases of primary and secondary infertility in both the groups showed no statistically significant difference. Multi-follicular development during induction was statistically significantly greater in the clomiphene group (1.27±1.11 versus 2.03±1.65; p=0.041). Ovulation occurred in 24 subjects (80%) in letrozole group and 18 subjects (60%) in the clomiphene group, with a statistically significant difference between the two groups (p=0.024). Pregnancy occurred in 16 subjects (53.33%) in letrozole group and 7 subjects (23.33%) in clomiphene group, which shows statistically significant difference between the two groups (p=0.048).Conclusions: Though number of developing follicles was found statistically significant with clomiphene citrate but ovulation rate and pregnancy rate were higher with letrozole group. Therefore, letrozole is a safe and better alternative for ovulation induction in patients of anovulatory PCOS, and it may be considered as a first line treatment for ovulation induction in these patients.

Clomiphene citrate versus letrozole for ovulation induction in anovulatory infertility: a prospective study

Background: The objective of this study was to compare clomiphene citrate with letrozole for ovulation induction in anovulatory infertile women.Methods: This study was conducted in the infertility clinic and department of obstetrics and gynecology, S.P. Medical College and Associated P. B. M. Hospital, Bikaner, Rajasthan, from 1st August 2018 to 31st July 2019. The study group comprised of infertile females attending infertility clinic or gynae outdoor in department of obstetrics and gynecology, S. P. Medical College Bikaner for infertility. 100 women with anovulatory infertility were enrolled in the study after fulfilling the inclusion and exclusion criteria. Proper counseling was done and written informed consent taken.Results: Ovulation rate was statistically significantly greater in letrozole group. Monofollicular development was statistically significant greater in let group (CC 18%, Let 66%). The endometrial thickness on the day of ßhCG administration in CC group was 7.40±1.08 mm and in let group was 8.20±0.82 mm. Letrozole treated cases had better trilaminar pattern of endometrium as compared to clomiphene. The pregnancy rate was higher in letrozole group.Conclusions: As compare to clomiphene, letrozole is associated with higher pregnancy rate and ovulation rates among infertile women with anovulation.

Letrozole: an emerging array of hope for infertile women

Ovulation induction has been a major breakthrough in the management of female infertility since many decades. Letrozole, an aromatase inhibitor has been used as a potential therapy for ovulation induction. A large number of clinical evidences have been emerging which cite the beneficial role of Letrozole in conditions like anovulatory infertility, polycystic ovary syndrome (PCOS), unexplained infertility and an incipient role in endometriosis- related infertility with regards to higher live-birth rates. Letrozole is a superior alternative to Clomiphene citrate (CC) which has been used conventionally as ovulation inducer. Clomiphene citrate has certain well-defined disadvantages, whereas Letrozole overcomes these limitations to a reasonable extent. The peripheral anti-estrogenic effect of CC leads to prolonged depletion of estrogens receptors, adversely affecting endometrial growth and development as well as quantity and quality of cervical mucus. Persistent blockade of estrogen receptor leads to CC resistance and is associated with reduced ovulation and pregnancy rates. Available evidences suggest Letrozole is superior to CC owing to the lack of persistent anti-estrogenic action due to its short half- life and lack of action on estrogen receptors. This typically leads to monofollicular growth and also higher live birth rates. The current evidences suggest that Letrozole can be placed as first line therapy for the management of infertility due to PCOS and unexplained infertility.

Effects of clomiphene citrate on seminal parameters in idiopathic oligospermia: a single blinded prospective randomized controlled trial

Background: About 15% married couples face problem of infertility of which male factor is implicated in 20% of them. In about 30% infertile men no causative factor is found and the condition is termed “Idiopathic”. They are often treated by empirical medications or Assisted Reproductive Technologies (ART) although success in few; our present study is carried on effects of clomephene citrate on seminal parameters in idiopathic oligospermia.Methods: This single blinded prospective randomized controlled trial was conducted at the infertility clinic with 200 idiopathic oligospermic men (sperm count <15 millions/ ml of ejaculate) after fulfilling inclusion and exclusion criteria and were alternately allocated into two equal groups - “Group C” receiving clomephene citrate tablets and “ Group P” receiving placebo after concealment. Semen analysis data were collected at baseline and every month and three months of completion of treatment and were summarized by routine descriptive statistical analysis.Results: The demographic characteristics like mean age is comparative in both groups but duration of infertility of >2 years is more in group C than group p (4.3±3.06 versus 4.1±2.57). The semen volume, spermatozoa count, sperm motility and not normal form are all increased after three months of treatment in group C as are biochemical parameters like total testosterone and serum FSH, LH and as also pregnancy rate (22% versus 4%).Conclusions: This study showed clomiphene citrate treatment protocol is inexpensive, relatively safe and easy to administer and improves semen volume, sperm count and sperm motility but not sperm morphology by increasing serum testosterone, FSH and LH in male and resulting in improved pregnancy rate in female partners.

Management of Anabolic Steroid-Induced Infertility: Novel Strategies for Fertility Maintenance and Recovery

There is often inherent conflict in the overlapping fields of male fertility and andrology. While the goal of all male fertility specialists is to facilitate and preserve biologic paternity, many practitioners also care for a significant number of patients suffering from hypogonadism. Exogenous testosterone administration, the gold standard for the management of these patients, almost universally impairs spermatogenesis and can even completely eradicate it in some men. With steady increases in both the incidence of hypogonadism and average paternal age, practitioners are now encountering hypogonadal men who desire future fertility or men suffering the effects of earlier androgenic anabolic steroid use with increasing frequency. In this manuscript, we review management strategies for these complex patients and explore novel medications that may be of use in this population.

Demographics, Usage Patterns, and Safety of Male Users of Clomiphene in the United States

PURPOSE: The aim of this study was to characterize the demographics, usage patterns and complication rates of clomiphene use in male patients.MATERIALS AND METHODS: We retrospectively analyzed male patients from ages 20 to 55 years old who were prescribed clomiphene citrate from 2001 to 2014 using the Truven Health MarketScan, a US claims database. We collected data regarding associated medical diagnoses, diagnostic testing, duration of use, and reported side effects including thrombotic events, vision problems, gynecomastia, mental disorders, liver disease, nausea, or skin problems.RESULTS: In total, 12,318 men took clomiphene and represented the primary study cohort, with a mean age of 37.8 years. The percentage of men prescribed clomiphene increased over the study period, as did the average age of clomiphene users. Associated diagnoses included male infertility (52.0%), testicular hypofunction (13.5%), erectile dysfunction (2.4%), and low libido (0.4%). Associated testing included semen analysis (43.7%), testosterone (23.5%), luteinizing hormone (19.3%), and follicle-stimulating hormone (21.1%) levels. The median time of clomiphene use was 3.6 months, with 63% of men stopping within 6 months. No increased risk of reported clomiphene side effects were apparent in men taking the medication.CONCLUSIONS: There is a rising prevalence of clomiphene usage without associated adverse side effects in the US. The variability in associated diagnoses, diagnostic testing, and duration of use suggest a need for greater awareness of the proper evaluation and treatment of the men who are prescribed clomiphene.

Effect of liraglutide combined with clomiphene on serum sex hormone levels and natural conception rate in obese women with polycystic ovary syndrome / 中国基层医药

Objective@#To explore the effect of liraglutide combined with clomiphene on serum hormone levels and natural conception rate in obese patients with polycystic ovary syndrome.@*Methods@#A total of 89 infertile patients with obese polycystic ovary syndrome who were treated in the First People's Hospital of Jinzhong from April 2015 to March 2016 were selected.They were randomly divided into observation group(n=45) and control group (n=44) by simple randomization method.The control group was treated with clomiphene citrate, and the observation group was given liraglutide combined with clomiphene.The fasting blood glucose(FPG), glycosylated hemoglobin(HbAc1), BMI, follicle stimulating hormone(FSH), luteinizing hormone(LH), testosterone(T), total cholesterol(TC), triglyceride (TG), high-density lipoprotein(HDL-C), and low-density lipoprotein(LDL-C) before and after treatment were compared.The menstrual cycle rate, normal ovulation, normal conception, early embryo death, and incidence rate of adverse reaction were recorded after treatment.@*Results@#After treatment, the FPG, HbAc1 and BMI in the observation group were significantly lower than those in the control group(t1=4.144, t2=5.862, t3=5.403, all P<0.05). After treatment, the levels of FSH, LH and T in the observation group were lower than those in the control group(t1=5.972, t2=5.359, t3=6.603, all P<0.05). The levels of TC, TG and LDL-C in the observation group were significantly lower than those in the control group(t1=10.697, t2=5.344, t3=6.986, all P<0.05). The HDL-C of the observation group was higher than that of the control group(t=4.340, P<0.05). After treatment, the menstrual cycle rate, normal ovulation rate, natural conception rate of the observation group were 91.11%, 84.44%, 80.00%, respectively, which were higher than those of the control group (72.72%, 61.36%, 54.54%) (χ12=5.099, χ22=6.017, χ32=6.562, all P<0.05). The early embryo mortality rate of the observation group was 6.67%, which was lower than 27.27% of the control group (χ2=6.741, P<0.05). The total incidence of adverse reactions in the observation group was 8.89%, which was lower than 29.55% in the control group (χ2=6.143, P<0.05).@*Conclusion@#Liraglutide combined with clomiphene in the treatment of obese polycystic ovary syndrome infertility patients can effectively reduce the body weight, regulate blood lipids, glucose metabolism, sex hormone levels, improve the natural conception rate of patients, reduce the incidence of adverse reactions.Its effect is significant.

Effect of liraglutide combined with clomiphene on serum sex hormone levels and natural conception rate in obese women with polycystic ovary syndrome / 中国基层医药

Objective To explore the effect of liraglutide combined with clomiphene on serum hormone levels and natural conception rate in obese patients with polycystic ovary syndrome .Methods A total of 89 infertile patients with obese polycystic ovary syndrome who were treated in the First People's Hospital of Jinzhong from April 2015 to March 2016 were selected.They were randomly divided into observation group (n=45) and control group (n=44) by simple randomization method .The control group was treated with clomiphene citrate , and the observation group was given liraglutide combined with clomiphene .The fasting blood glucose ( FPG ) , glycosylated hemoglobin (HbAc1),BMI,follicle stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),total cholesterol (TC),triglyceride (TG),high-density lipoprotein(HDL-C),and low-density lipoprotein(LDL-C) before and after treatment were compared .The menstrual cycle rate ,normal ovulation ,normal conception ,early embryo death ,and incidence rate of adverse reaction were recorded after treatment .Results After treatment,the FPG,HbAc1 and BMI in the observation group were significantly lower than those in the control group ( t1 =4.144,t2 =5.862,t3 =5.403,all P<0.05).After treatment,the levels of FSH,LH and T in the observation group were lower than those in the control group(t1 =5.972,t2 =5.359,t3 =6.603,all P<0.05).The levels of TC,TG and LDL-C in the observation group were significantly lower than those in the control group (t1 =10.697,t2 =5.344,t3 =6.986,all P<0.05).The HDL-C of the observation group was higher than that of the control group (t=4.340,P<0.05).After treatment,the menstrual cycle rate,normal ovulation rate ,natural conception rate of the observation group were 91.11％,84.44％,80.00％, respectively,which were higher than those of the control group (72.72％,61.36％,54.54％) (χ21 =5.099,χ22 =6.017,χ23 =6.562,all P<0.05).The early embryo mortality rate of the observation group was 6.67％,which was lower than 27.27％ of the control group (χ2 =6.741,P<0.05).The total incidence of adverse reactions in the observation group was 8.89％,which was lower than 29.55％ in the control group (χ2 =6.143,P <0.05). Conclusion Liraglutide combined with clomiphene in the treatment of obese polycystic ovary syndrome infertility patients can effectively reduce the body weight ,regulate blood lipids ,glucose metabolism ,sex hormone levels ,improve the natural conception rate of patients ,reduce the incidence of adverse reactions .Its effect is significant .

Comparative evaluation of different cost effective ovulation induction drugs and their effect on follicular growth, endometrial thickness and pregnancy outcome

Background: Ovulatory dysfunction is a common cause of female infertility, occurring in up to 20 - 30% of infertile women. The most commonly prescribed ovulation drugs are clomiphene citrate (CC), tamoxifen, aromatase inhibitors (such as letrozole) and gonadotropins. Objective of the study was to evaluate the efficacy of clomiphene citrate, letrozole and tamoxifen for ovulation induction in anovulatory infertility.Methods: Randomized open label interventional clinical trial. Patients were randomized to 3 drug groups. After baseline investigations, they were subjected to ovulation induction and then USG monitoring of follicular growth and ovulation. The primary outcome measured was occurrence of conception. Secondary outcome was effect on endometrial thickness and ovulation rate.Results: In the study, letrozole group showed 100% mono-follicular response. Mid cycle endometrial thickness in about 17% of cases in CC group is ≤8 mm. But all the cases in tamoxifen and letrozole group have ET >8 mm. This difference is statistically significant. The ovulation and conception rates are highest in letrozole group but the difference was not statistically significant.Conclusions: Letrozole produces higher mid cycle endometrial thickness, 100% mono follicular development than clomiphene and tamoxifen. This difference is found to be statistically significant. Ovulation rate and conception rate is highest in letrozole group. But there is no statistically significant difference among the three drugs.

Clomiphene citrate plus N-acetyl cysteine versus letrozole for induction of ovulation in infertile patients with polycystic ovarian disease: a randomized clinical trial

Background: Polycystic ovarian disease (PCOD), a common endocrine disorder with multisystem affection, is the most common cause of anovulatory infertility. Our objective is to evaluate the effect of using clomiphene citrate (CC) plus N-acetyl cysteine (NAC) versus letrozole in ovulation induction in infertile patients with PCOD.Methods: Reproductive-aged infertile women either primary or secondary diagnosed as PCOD according to Rotterdam criteria, 2003 were considered for enrollment. Eligible women for were recruited and randomized (1:1) to receive either CC 100 mg plus NAC 600 mg (CC+NAC arm) or letrozole 5 mg (NCT03241472, clinicaltrials.gov). All medications were started from day 3 of the menstrual cycle for 5 days. The primary outcome was the ovulation rate in both groups. Secondary outcomes included the mid-cyclic endometrial thickness, ovarian hyperstimulation, and clinical pregnancy and miscarriage rates.Results: One hundred ten patients were enrolled and randomized to CC+NAC arm (n=55) or letrozole (n=55). The ovulation rate in patients in letrozole arm was significantly higher than CC+NAC arm (71.8% versus 53.2%, p=0.01). Additionally, endometrial thickness was higher in letrozole arm (mean±SD: 11.46±1.61 versus 9.0±1.13, p=0.031). However, no statistical significant difference with regarding the ovarian hyperstimulation rate (1.8% versus 3.6%, p=0.157), clinical pregnancy rate [3/19 patients (27.3%) versus 19/55 (34.5%), p=0.409] and miscarriage rate [4/15 patients (26.7%) versus 19/55 (15.8%), p=0.317] in CC+NAC versus letrozole groups respectively.Conclusions: Addition of NAC to CC in ovulation induction leads to comparable pregnancy rate as letrozole. However, letrozole produces high ovulation rate and the better mid-cyclic endometrial thickness.

Therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of polycystic ovary syndrome

SUMMARY OBJECTIVE In view of the high incidence of polycystic ovary syndrome (PCOS) and the unsatisfactory therapeutic effects of dimethyldiguanide or clomifene citrate alone, our study aimed to investigate the therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of PCOS. METHODS A total of 79 patients with POCS and 35 healthy females were included, and endometrial biopsies were obtained. The sterol regulatory element-binding protein-1 (SREBP1) expression in endometrial tissues was detected by qRT-PCR. POC patients were randomly divided into group A (n=40) and group B (n=39). Patients in group A were treated with dimethyldiguanide combined with clomifene citrate, while patients in group B were treated with clomifene citrate alone. The number of mature follicles and cervical mucus score, follicular development rate and single follicle ovulation rate, cycle pregnancy rate, early miscarriage rate, ovulation rate, endometrial thickness, positive rate of three lines sign, follicle stimulating hormone level and luteinizing hormone level were compared between the two groups. RESULTS The expression level of SREBP1 was higher in PCOS patients than that in the healthy control. SREBP1 expression was inhibited after treatment, while the inhibitory effects of combined treatment were stronger than those of clomifene citrate alone. Compared with clomifene citrate alone, the combined treatment improved cervical mucus score, follicle development rate, single follicle ovulation rate, endometrial thickness, positive rate of three lines sign, and follicle-stimulating hormone level. CONCLUSION The therapeutic effect of combined treatment is better than clomifene citrate alone in the treatment of PCOS.

RESUMO OBJETIVO Tendo em vista a alta incidência de síndrome dos ovários policísticos (SOP) e os efeitos terapêuticos insatisfatórios da dimetildiguanida ou do citrato de clomifeno isoladamente, nosso estudo teve como objetivo investigar os efeitos terapêuticos da dimetildiguanida associada ao citrato de clomifeno no tratamento da SOP. MÉTODOS Um total de 79 pacientes com POCS e 35 mulheres saudáveis foram incluídos, e biópsias endometriais foram obtidas. A expressão da proteína de ligação do elemento regulador de esterol-1 (SREBP1) nos tecidos endometriais foi detectada por qRT-PCR. Pacientes POC foram divididos aleatoriamente em grupo A (n=40) e grupo B (n=39). Os pacientes do grupo A foram tratados com dimetildiguanida combinada com citrato de clomifeno, enquanto os pacientes do grupo B foram tratados apenas com citrato de clomifeno. O número de folículos maduros e muco cervical, taxa de desenvolvimento folicular e taxa de ovulação, taxa de gravidez, abortamento precoce, taxa de ovulação, espessura endometrial, taxa positiva de três linhas, nível de hormônio folículo estimulante e nível de hormônio luteinizante foram comparados entre os dois grupos. RESULTADOS O nível de expressão do SREBP1 foi maior nos pacientes com SOP do que no controle normal. A expressão de SREBP1 foi inibida após o tratamento, enquanto os efeitos inibidores do tratamento combinado foram mais fortes do que os do citrato de clomifeno isoladamente. Comparado com o citrato de clomifeno sozinho, o tratamento combinado melhorou significativamente a pontuação do muco cervical, a taxa de desenvolvimento folicular, a taxa de ovulação do folículo único, a espessura endometrial, a taxa positiva de três linhas de sinal e o nível de hormônio folículo estimulante. CONCLUSÃO O efeito terapêutico do tratamento combinado é melhor do que o citrato de clomifeno isolado no tratamento da SOP.

Comparative study of laparoscopic ovarian drilling and medical treatment in polycystic ovarian disease

Background: To evaluate the result after medical treatment and laparoscopic ovarian drilling in PCOS patients and to compare the results of these two methods.Methods: In this prospective study 50 women with polycystic ovarian disease, were divided into two group,25 women received medical treatment and 25 women received surgical (laparoscopic ovarian drilling) treatment. Effect of treatment on ovulation, menstruation, fertility and androgen level was determined 3 month after therapy.Results: There was significant increase in ovulation and fertility, decrease in androgen levels and decrease in LH/FSH in individual groups when compared with pretreatment levels but difference between groups A and B was not statistically significant for these parameters.Conclusions: Medical treatment and laparoscopic ovarian drilling are equally effective in treating the women of polycystic ovarian disease. Result of both the treatment are similar in this study. However medical treatment should be the first line therapy, it has significant benefit for use in OPD, low cost, no hospital stays and convenience to the patient.

A study for evaluation of two protocols comprising of clomiphene citrate, human menopausal gonadotropin with or without follicle stimulating hormone for ovulation induction in patients with infertility for intrauterine insemination

Background: To compare two protocols comprising of FSH/CC/HMG and CC/HMG for ovulation induction and IUI in women with infertility.Methods: 60 women with unexplained infertility were randomized using sequentially numbered opaque envelope method. Group A received inj FSH 150 units on day 2 of menstrual cycle and clomiphene citrate 100 mg from day 3-7, followed by injection HMG 150 units on day 9 of menstrual cycle. Group B received clomiphene citrate 100 mg from day 3-7, and HMG 150 units on day 7 and 9 of the menstrual cycle.  Ovulation triggered with hCG 5000 units when dominant follicle was 18mm. Single IUI was done 36-42 hours afterwards.Results: Pregnancy occurred in 3 out of 30 women in 116 cycles Group A (with FSH) with a pregnancy rate of 10 percent, and 2.8% per cycle. In group B (without FSH) pregnancy occurred in 3 out of 30 women in 117 cycles with pregnancy rate of 10 percent, and 2.6% per cycle. The number of follicles per cycle was 1.36 and follicle size was 18.57 mm in group A. While in Group B numbers of follicles per cycle were 1.22, with average size of 18.9mm. Mean endometrial thickness was 7.7mm in Group A and 6.37 in Group B (p=.01, significant). Mild OHSS was observed in one woman in Group B. No other side effects were observed in both the groups.Conclusions: The controlled ovarian stimulation regimes used in this study are equally effective, easy to administer, require less intensive monitoring and fewer medications, with little risk of OHSS and multiple gestation.