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The objective: to study the effect of stimulating hormone therapy on the condition of the mammary glands depending on the initial endocrine status of women with menstrual disorders in the background and after ovulation stimulation.Materials and methods. The study selected a group of 130 patients (n=130) of reproductive age (mean age 27±2,3 years), which by the nature of menstrual disorders are divided into 2 subgroups: 1 subgroup (n=57) – women with regular menstrual rhythm and insufficiency of the luteal phase (ILP), 2 subgroup (n=73) – women with secondary amenorrhea and oligomenorrhea on the background of chronic anovulation. All patients complained of no pregnancy for an average of 4±1,2 years. After a comprehensive assessment of the reproductive system and hormone-dependent organs, women received the proposed treatment with estrogen-progestogen drug, bromocriptine and ovulation stimulation with clomifene citrate.Results. During the preparatory (diagnostic) phase of the study it was found that in 1 subgroup in 89,5% of patients with concomitant diseases of the pelvic organs and only endocrine disorders of the ILP type in 10,5%. In women of 2 subgroup, the frequency of combined pathology was 23,3%, and endocrine disorders – 76,7%. These results confirmed the need for laparoscopic and hysteroscopic examination of all patients with infertility in addressing the issue of ovulation stimulation. After short cycles (3 months) of monophasic estrogen-progestogen therapy, 31,6% of patients with ILP and 17,1% with anovulation had a positive effect on reducing the incidence of pain in the mammary glands, with the most sensitive to therapy were patients with diffuse forms of fibrocystic disease with a predominance of cystic and glandular components. When resuming biphasic ovulatory cycles with clomifene citrate stimulation, only 5,7% of women complained of breast pain during the first 1–2 cycles. No additional foci in the subgroups were detected, and previously diagnosed fibroadenomas did not increase.Conclusion. Analyzing the obtained data, a positive effect of different types of hormone therapy on the condition of the mammary glands in patients with menstrual and reproductive dysfunction, in particular with diffuse forms of fibrocystic disease with a predominance of cystic and glandular components, is structures most sensitive to normal progesterone levels. Despite the lack of negative dynamics on the background of ovulation stimulation and restoration of normal mammary gland structure after therapy in women with menstrual disorders of endocrine origin, menstrual cycle regulation and dynamic monitoring of the mammary glands are shown to prevent the development of hyperplastic processes.

Clomifene citrate has long been associated with a multiple pregnancy rate of up to 8-10%. Studies from which these figures originated have largely included patients who received clomifene outside of current national and international treatment guidelines. In January 2020, a systematic review of MEDLINE and relevant reference lists was conducted. Studies were included that reported multiple pregnancy rate in a cohort of patients undergoing treatment with single agent clomifene citrate for WHO group II dysovulatory subfertility. Twelve studies were included in the analysis, with a total sample size of 1,387 patients. The overall multiple pregnancy rate was 3.8% (3.6% twins/0.2% triplets); this dropped to 2.4% (all twins) when studies with a mean BMI ≥35kg/m2 were excluded. This review suggests that contemporary single agent clomifene use following current guidelines in terms of indication, results in a lower than expected multiple pregnancy rate. Further evidence from clinical practice is required to ensure that patients are adequately informed.

The objective. To analyze the results of ovulation stimulation and restoration of reproductive function in women with breast pathology with endocrine infertility.Materials and methods. For the study, a group of 130 patients (n=130) of reproductive age (mean age 27±2,3 years) was selected, who were divided into 2 subgroups by the nature of menstrual dysfunction: 1 subgroup (n=57) – women with a regular rhythm of the menstrual cycle and insufficiency of the luteal phase, 2 subgroup (n=73) – women with secondary amenorrhea and oligomenorrhea against the background of chronic anovulation. All patients complained about the absence of pregnancy for an average of 4±1,2 years. After a comprehensive assessment of the state of the reproductive system and hormone-dependent organs, women received therapy with an estrogen-progestin drug, bromocriptine and stimulation of ovulation with clomifene.Results. The study found that menstrual irregularities in all patients were due to endocrine pathology: a regular rhythm in combination with luteal phase insufficiency – 43,8%, secondary amenorrhea and oligomenorrhea against the background of chronic anovulation – 56,2%. Examination of the mammary glands in 66,9% of patients revealed various variants of fibrocystic disease. Primary infertility was diagnosed in 87 patients (66,9%), secondary – in 43 (33,1%). In 1 subgroup 89,5% of cases had concomitant diseases of the pelvic organs, endocrine disorders of the type of luteal phase insufficiency in 10,5%. In patients of 2 subgroup, the incidence of combined pathology was 23,3%, and endocrine disorders – 76,7%.These results confirmed the need for endoscopic examination of all patients with infertility when deciding whether to stimulate ovulation. After gradual therapy with the inclusion in the program of laparoscopy, hysteroscopy, COCs, bromocriptine and stimulation of ovulation with clomifene, it was possible to restore reproductive function in 1 subgroup in 33,3%, in 2 subgroup – in 40%. In patients with hyperprolactinemia on the background of bromocriptine, ovulation was restored in 73,7%.Conclusion. Analysis of the reproductive function of women with breast pathology with endocrine infertility proves that in almost every 2nd patient, menstrual-reproductive dysfunction arose under the influence of various factors after the establishment of a regular rhythm of menstruation, which indicates the initial imperfect level of neuroendocrine structures involved in regulation these processes in this contingent of patients. An increase in the incidence of primary infertility by 1,5–2 times compared with secondary is characteristic for the group of patients with endocrine forms of infertility.With clomifene stimulation, almost a third of the surveyed contingent managed to restore the biphasic ovulatory cycle, improve reproductive function and reduce pain in the mammary glands, which allows us to conclude that complete hormonal screening and clarification of the causes of menstrual irregularities before prescribing hormonal therapy are necessary., Цель исследования: анализ результатов стимуляции овуляции и восстановления репродуктивной функции у женщин с патологией грудных желез при эндокринном бесплодии.Материалы и методы. Для исследования отобрана группа из 130 больных репродуктивного возраста, которых по характеру нарушений менструальной функции разделили на две подгруппы: 1-я подгруппа (n=57) – женщины с регулярным ритмом менструального цикла и недостаточностью лютеиновой фазы (НЛФ), 2-я подгруппа (n=73) – женщины с вторичной аменореей и олигоменореей на фоне хронической ановуляции. Все больные предъявляли жалобы на отсутствие беременности в среднем в течение 4±1,2 года. После комплексной оценки состояния репродуктивной системы и гормонально зависимых органов женщины получали терапию с использованием эстроген-гестагенного препарата, бромкриптина и стимуляцию овуляции кломифеном.Результаты. В ходе исследования установлено, что нарушения менструального цикла у всех больных были обусловлены эндокринной патологией: регулярный ритм в сочетании с НЛФ – 43,8%, вторичная аменорея и олигоменорея на фоне хронической ановуляции – 56,2%. При обследовании грудных желез у 66,9% пациенток выявлены различные варианты фиброзно-кистозной болезни (ФКБ). Первичное бесплодие диагностировано у 87 (66,9%) пациенток, вторичное – у 43 (33,1%). В 1-й подгруппе в 89,5% случаев обнаружены сопутствующие заболевания органов малого таза, эндокринные нарушения по типу НЛФ – у 10,5%. У пациенток 2-й подгруппы частота сочетанной патологии составила 23,3%, а эндокринных нарушений – 76,7%.Такие результаты подтвердили необходимость эндоскопического обследования всех больных с бесплодием при решении вопроса о стимуляции овуляции. После поэтапной терапии с включением в программу лапароскопии, гистероскопии, КОК, бромкриптина и стимуляцию овуляции кломифеном восстановить репродуктивную функцию удалось в 1-й подгруппе у 33,3%, во 2-й подгруппе – у 40% женщин. У пациенток с гиперпролактинемией на фоне бромкриптина восстановлена овуляция в 73,7% случаев.Заключение. Анализ репродуктивной функции женщин с патологией грудных желез при эндокринном бесплодии доказывает, что практически у каждой второй больной нарушения менструально-репродуктивной функции возникали под воздействием различных факторов после установления регулярного ритма менструаций. Это свидетельствует об исходном несовершенном уровне нейроэндокринных структур, принимающих участие в регуляции этих процессов у данного контингента больных. Увеличение частоты первичного бесплодия в 1,5–2 раза по сравнению с вторичным характерно для группы больных с эндокринными формами бесплодия.При стимуляции кломифеном почти у трети обследуемого контингента удалось восстановить двухфазный овуляторный цикл, улучшить репродуктивную функцию и уменьшить болевые ощущения в грудных железах, что позволяет сделать вывод о необходимости полного гормонального скрининга и уточнения причин нарушения менструального цикла перед назначением терапии гормональными препаратами., Мета дослідження: аналіз результатів стимуляції овуляції і відновлення репродуктивної функції у жінок із патологією грудних залоз при ендокринному безплідді.Матеріали та методи. Для дослідження відібрано групу зі 130 хворих репродуктивного віку, яких за характером порушень менструальної функції розподілено на дві підгрупи: 1-а підгрупа (n=57) – жінки з регулярним ритмом менструального циклу і недостатністю лютеїнової фази (НЛФ); 2-а підгрупа (n=73) – жінки з вторинною аменореєю і олігоменореєю на фоні хронічної ановуляції. Усі хворі скаржились на відсутність вагітності у середньому протягом 4±1,2 року. Після комплексного оцінювання стану репродуктивної системи і гормонально залежних органів жінки отримували терапію з використанням естроген-гестагенного препарату, бромкриптину і стимуляцію овуляції кломіфеном.Результати. У ході дослідження встановлено, що порушення менструального циклу у всіх хворих були зумовлені ендокринною патологією: регулярний ритм у поєднанні з НЛФ – 43,8%, вторинна аменорея і олігоменорея на фоні хронічної ановуляції – 56,2%. При обстеженні грудних залоз у 66,9% пацієнток виявлені різні варіанти фіброзно-кістозної хвороби (ФКХ). Первинне безпліддя діагностовано у 87 (66,9%) пацієнток, вторинне – у 43 (33,1%). У 1-й підгрупі у 89,5% випадків спостерігались супутні захворювання органів малого таза, ендокринні порушення за типом НЛФ – у 10,5%. У пацієнток 2-ї підгрупи частота поєднаної патології становила 23,3%, а ендокринних порушень – 76,7%.Такі результати підтвердили необхідність ендоскопічного обстеження всіх хворих із безпліддям при вирішенні питання про стимуляцію овуляції. Після поетапної терапії з включенням до програми лапароскопії, гістероскопії, КОК, бромкриптину і стимуляцію овуляції кломіфеном відновити репродуктивну функцію вдалося у 1-й підгрупі у 33,3%, у 2-й підгрупі – у 40% жінок. У пацієнток з гіперпролактинемією на фоні бромкриптину було відновлено овуляцію у 73,7% відповідно.Заключення. Аналіз репродуктивної функції жінок із патологією грудних залоз при ендокринному безплідді доводить, що практично у кожної другої хворої порушення менструально-репродуктивної функції виникали під впливом різних факторів після встановлення регулярного ритму менструацій. Це свідчить про вихідний недосконалий рівень нейроендокринних структур, які беруть участь в регуляції цих процесів у даного контингенту хворих. Підвищення частоти первинного безпліддя в 1,5–2 разу порівняно з вторинним характерно для групи хворих з ендокринними формами безпліддя.Під час стимуляції кломіфеном майже у треті обстежуваного контингенту вдалося відновити двофазний овуляторний цикл, покращити репродуктивну функцію і зменшити больові відчуття у грудних залозах, що дозволяє зробити висновок про необхідність повного гормонального скринінгу й уточнення причин порушення менструального циклу перед призначенням терапії гормональними препаратами.

It has been reported that the antiestrogen Tamoxifen induces liver tumors in rats and genotoxic effects in vitro through DNA interaction. So, it can be proposed that its structural analogue, Clomifene, also can bind to DNA. To test this hypothesis, the DNA binding properties of Clomifene have been studied by absorption spectroscopy, fluorescence spectroscopy, cellular uptake, cell viability, cell proliferation and molecular modeling techniques. Evidences are provided that Clomifene could interact with DNA via minor groove interaction mode. The negative ΔG value implied that the interaction occurred between DNA and Clomifene spontaneously. Also, the positive ΔH and positive ΔS values indicated that the binding of Clomifene with DNA is mainly entropy driven and the enthalpy is unfavorable parameter. This also suggests that the hydrophobic interaction plays a major role in the binding with overall binding constant of K=5.645×107M-1 at 298K. From the results of docking, it can be concluded that Hydrogen bonds is also one of the most important interactions. The increase in entropy of system after binding might be due to the destruction of the DNA structure.

Isocitrate dehydrogenase (IDH) plays an indispensable role in the tricarboxylic acid cycle, and IDH mutations are present in nearly 75% of glioma and 20% of acute myeloid leukemia. One IDH1R132H inhibitor (clomifene citrate) was found by virtual screening method, which can selectively suppress mutant enzyme activities in vitro and in vivo with a dose-dependent manner. The molecular docking indicated that clomifene occupied the allosteric site of the mutant IDH1. Enzymatic kinetics also demonstrated that clomifene inhibited mutant enzyme in a non-competitive manner. Moreover, knockdown of mutant IDH1 in HT1080 cells decreased the sensitivity to clomifene. In vivo studies indicated that clomifene significantly suppressed the tumor growth of HT1080-bearing CB-17/Icr-scid mice with oral administration of 100 mg/kg and 50 mg/kg per day. In short, our findings highlight clomifene may have clinical potential in tumor therapies as a safe and effective inhibitor of mutant IDH1.

A prospective observational study was conducted on 186 patients with clomifene citrate (CC)-resistant polycytic ovary syndrome (PCOS) who were allocated into two treatment arms for three months; letrozole alone (n = 92) and letrozole with luteal support using vaginal dydrogestrone (n = 94). Patients received luteal support experienced significantly higher clinical pregnancy rate than those who received letrozole alone (48.9% vs. 23.9%, respectively). Luteal support in letrozole treated CC-resistant PCOS significantly improves pregnancy rate and should be implemented in ovulation induction regimens.

Mitochondria continually move, fuse and divide, and these dynamics are essential for the proper function of the organelles. Indeed, the dynamic balance of fusion and fission of mitochondria determines their morphology and allows their immediate adaptation to energetic needs as well as preserving their integrity. As a consequence, mitochondrial fusion and fission dynamics and the proteins that control these processes, which are conserved from yeast to human, are essential, and their disturbances are associated with severe human disorders, including neurodegenerative diseases. For example, mutations in OPA1, which encodes a conserved factor essential for mitochondrial fusion, lead to optic atrophy 1, a neurodegeneration that affects the optic nerve, eventually leading to blindness. Here, by screening a collection of ∼1600 repurposed drugs on a fission yeast model, we identified five compounds able to efficiently prevent the lethality associated with the loss of Msp1p, the fission yeast ortholog of OPA1. One compound, hexestrol, was able to rescue both the mitochondrial fragmentation and mitochondrial DNA (mtDNA) depletion induced by the loss of Msp1p, whereas the second, clomifene, only suppressed the mtDNA defect. Yeast has already been successfully used to identify candidate drugs to treat inherited mitochondrial diseases; this work may therefore provide useful leads for the treatment of optic atrophies such as optic atrophy 1 or Leber hereditary optic neuropathy., Editor's choice: Mitochondria are conserved among eukaryotes and mutations in the factors that control their dynamics are causal for various human disorders. Hence, yeast models can be used for pharmacological screenings.

PKOS'lu kadınlardan oosit elde edilmesinin zorluğu göz önüne alındığında, deneysel PKOS modeli oluşturulduktan sonra elde edilen oositlerin, maturasyon çalışmalarına olanak sağlaması ve bu çalışmalardan elde edilecek verilerin gelecekte infertilite tedavisine katkı sağlayabilecek olmasından dolayı büyük önem taşımaktadır. Bu çalışmada deneysel PKOS fare modelinde farklı ilaç uygulamalarından sonra oosit maturasyonunu etkileyen faktörlerin değerlendirilmesi amaçlanmıştır. Dört haftalık dişi Balb/C farelerde deneysel PKOS modeli 21 gün boyunca 6 mg/100g DHEA verilerek oluşturuldu. PKOS modeli oluşturulan farelerde sadece klomifen sitrat ya da klomifen sitrat, metformin ve pioglitazon kombine olarak uygulandıktan sonra oosit maturasyonunu etkileyen Cep55, Cdk4, Hsp27, Nobox, Foxl2, Cx37, Cx43, Adamts-1 ve Adamts-9 belirteçlerinin değişimleri hem ovaryumlarda hem de oositlerde immunoperoksidaz ve immunofloresan yöntemleri kullanılarak değerlendirildi. Histolojik ve morfolojik bulgular ile PKOS modelinin geliştiği gösterildi. PKOS grubunda ovaryumlarda özellikle sekonder foliküllerde ve oositlerde oosit maturasyonunu etkileyen belirteçlerin azaldığı, tedavi gruplarından elde edilen ovaryumlarda sekonder ve tersiyer foliküllerde ve oositlerde belirteçlerin ekspresyonlarının arttığı gözlendi. Sadece klomifen sitrat ile tedavi uygulanan grupta ekspresyonların kombine tedavi grubuna göre daha fazla artmış olduğu tespit edildi. PKOS grubunda bu belirteçlerin ekspresyonunun azalması ve tedavi gruplarında artmış olması, karmaşık moleküler mekanizmaya sahip olan oosit maturasyonunda, yeni moleküllerin gösterilmesi açısından önemlidir. Aynı belirteçlerin daha ileri teknikler ile incelenmesi PKOS'lu olgularda bu belirteçlerin oosit maturayonunda kullanılacak yeni moleküller olacağını düşündürmektedir. Considering the difficulty of obtaining oocytes from women with PCOS, it is of great importance that the oocytes obtained after the experimental PCOS model has been established allow for maturation studies and that the data from these studies may contribute to future infertility treatment. The aim of this study was to evaluate the factors affecting oocyte maturation after different drug applications in experimental PCOS mouse model. In four weeks old female Balb/C mice, the experimental PCOS model was generated by administration 6 mg/100g DHEA for 21 days. In the PCOS model mice after the administrations of only clomiphene citrate or clomiphene citrate, metformin and pioglitazone combined treatments, the changings of markers which affect the oocyte maturation Cep55, Cdk4, Hsp27, Nobox, Foxl2, Cx37, Cx43, Adamts-1 and Adamts-9 were evaluated in both ovaries and oocytes using immunoperoxidase and immnuofluorescent methods. The histological and morphological findings showed that the PCOS model was developed. In PCOS group, it was observed that the markers affecting oocyte maturation decreased in ovaries, especially in secondary follicles and oocytes, and in the ovaries of treatment groups the expression of markers in secondary and tertiary follicles and oocytes were increased. It was found that only Clomiphene Citrate treated group had higher expressions than the combined treatment group. The decrease in the expression of these markers in the PCOS group and the increase in the treatment groups is important for demonstrating new molecules in oocyte maturation with a complex molecular mechanism. Examining the same markers with more advanced techniques suggests that these markers will be new molecules to be used in oocyte maturation in PCOS patients. 168

Aim — to investigate the methods of treatment, directed on increase in quantity of spermatozoa in an ejaculate.Material and methods. In investigation was used: chorionic gonadotrophin, anti-estrogen, recombinant preparations FSH, and also their combinations.Results. The worst efficiency (10%) was noted when using monotherapy by preparation HCG. Efficiency of monotherapy by a preparation of clomiphene was higher and made 20% concerning conception, and 63% concerning an oligoteratozoospermiya. Efficiency of the combined therapy of HCG in combination with recombinant FSH was 40% concerning conception, and 87% concerning an oligoteratozoospermiya.Conclusion. At the same time the studied types of the stimulating therapy are effective, safe and don’t lead to development of side effects.

Objective To compare the effects of letrozole (2.5 mg) and anastrozole (1 mg) meant for ovulation induction in clomiphene (CC)-resistant women with PCOS. Design Prospective randomized trial. Setting University teaching hospital and private practice setting. Patient(s) The study comprised a total of 220 infertile women (574 cycles) with CC-resistant PCOS. Intervention(s) Patients were randomized to treatment with 2.5 mg of letrozole daily (111 patients, 295 cycles) or 1 mg of anastrozole daily (109 patients, 279 cycles) for 5 days from day 3 of menses. Main Outcome Measure(s) Number of follicles, serum E 2 , serum P, endometrial thickness, pregnancy rate (PR), and miscarriage rate. Result(s) The total number of follicles was significantly more in the anastrozole group (5.4 ± 0.4 vs. 5.8 ± 0.4). The number of follicles ≥14 mm (3.1 ± 0.3 vs. 2.7 ± 0.2) and ≥18 mm (2.3 ± 0.1 vs. 3.1 ± 0.2) were significantly higher in the anastrozole group. The endometrial thickness at the time of hCG administration was significantly more in the anastrozole group (9.1 ± 0.2 vs. 10.2 ± 0.7 mm). The duration to reach a dominant follicle was longer in the letrozole group (12.1 ± 1.3 days vs. 8.8 ± 1.9 days) but without statistical significant difference. Ovulation occurred in 183/295 cycles (62%) in the letrozole group and 177/279 cycles (63.4%) in the anastrozole group, whereas pregnancy occurred in 36/295 cycles (12.2%) in the letrozole group and 42/279 cycles (15.1%) in the anastrozole group and the differences were not statistically significant. Conclusion(s) The results of this study did not show a significant difference in PR or miscarriage rate between anastrozole and letrozole when used for ovulation induction in women with CC-resistant PCOS.

Objective To compare clomiphene citrate (CC) and letrozole used for superovulation before intrauterine insemination (IUI) in unexplained infertility. Design Prospective randomized trial. Setting A university teaching hospital and a private practice setting. Patient(s) Four hundred and twelve infertile women with unexplained infertility. Intervention(s) Patients were randomized to treatment with 100 mg of CC daily (207 patients, 404 cycles) or 5 mg of letrozole daily (205 patients, 400 cycles) for 5 days starting on day 3 of menses. The IUI was done 36 ± 4 hours after human chorionic gonadotropin (hCG) injection. Main Outcome Measure(s) Number of follicles, serum estradiol level, serum progesterone level, endometrial thickness, and pregnancy and miscarriage rates. Result(s) The total number of follicles during stimulation was statistically significantly greater in the CC group (3.1 ± 0.36 vs. 1.6 ± 0.41). There was no statistically significant difference in pretreatment endometrial thickness between the two groups or endometrial thickness at the time of hCG administration. Serum E 2 and progesterone concentrations were statistically significantly higher in the CC group. The days to hCG injection were similar in both groups. Pregnancy occurred in 73 out of 205 patients (400 cycles) in the letrozole group (35.6% and 18.2%, respectively) and 78 out of 207 patients (404 cycles) (37.6% and 19.3%, respectively) in the CC group; the differences were not statistically significant. Two twin pregnancies occurred in the CC group. Conclusion(s) This study found no superiority between letrozole and CC for inducing ovulation in women with unexplained infertility before IUI.

Objective To compare the effect of letrozole with combined metformin and clomiphene citrate (CC) for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS). Design A randomized controlled trial. Setting University teaching hospital and a private practice setting. Patient(s) Two hundred fifty anovulatory women (582 cycles) with CC-resistant PCOS. Intervention(s) Patients received 2.5 mg of letrozole daily (123 patients, 285 cycles) or combined metformin–CC (127 patients, 297 cycles) for three treatment cycles. Main Outcome Measure(s) Ovulation rate, number of follicles, serum E 2 , serum P, endometrial thickness, pregnancy, and miscarriage rates. Result(s) Ovulation occurred in 185/285 cycles (64.9%) in the letrozole group versus 207/297 cycles (69.6%) in the combined metformin–CC group, without statistically significant difference. The total number of follicles was significantly more in the combined metformin–CC group (4.4 ± 0.4 vs. 6.8 ± 0.3). A nonsignificant increase in endometrial thickness on the day of hCG administration was observed in the letrozole group (9.5 ± 0.2 mm vs. 9.1 ± 0.1 mm). No statistically significant difference regarding the pregnancy rate (PR) was observed between both groups (14.7% vs. 14.4%). Conclusion(s) Letrozole and combined metformin–CC are equally effective for inducing ovulation and achieving pregnancy in patients with CC-resistant PCOS.

Objective To compare the effects of letrozole (5 mg) and clomiphene citrate (100 mg) for ovulation induction in women with polycystic ovary syndrome (PCOS). Design Prospective randomized trial. Setting University teaching hospital and private practice setting. Patient(s) The study comprised a total of 438 infertile women (1063 cycles) with PCOS. Intervention(s) Patients were randomized to treatment with 5 mg of letrozole daily (218 patients, 545 cycles) or 100 mg of clomiphene citrate daily (220 patients, 518 cycles) for 5 days starting on day 3 of menses. Timed intercourse was advised 24 to 36 hours after hCG injection. Main Outcome Measure(s) Number of follicles, serum estradiol, serum progesterone, endometrial thickness, and pregnancy and miscarriage rates. Result(s) The mean age, parity, and duration of infertility in both groups were similar. The total number of follicles was statistically significantly greater in the clomiphene citrate group (6.8 ± 0.3 versus 4.4 ± 0.4). Endometrial thickness at the time of hCG administration was statistically significantly greater in the CC group (9.2 ± 0.7 mm versus 8.1 ± 0.2 mm). The duration to reach a dominant follicle was statistically significantly longer in the letrozole group (12.1 ± 1.3 versus 8.8 ± 2.9 days). Ovulation occurred in 365 out of 540 cycles (67.5%) in letrozole group and 371 out of 523 cycles (70.9%) without a statistically significant difference. Levels of serum estradiol and progesterone were statistically significantly higher in the clomiphene citrate group. The pregnancy rate per cycle was 15.1% in the letrozole group and 17.9% in the clomiphene citrate group without statistically difference between the groups. Conclusion(s) The results of this study did not show any advantage to the use of letrozole over clomiphene citrate as a first-line treatment for induction of ovulation in women with PCOS.

The National Institute for Health and Care Excellence Clinical Guideline 156 advises that transvaginal ultrasonography (TVUS) should be used in the first cycle of treatment with clomifene citrate, to assess for multifollicular development and hence the risk of multiple pregnancy. This guidance is based on expert opinion rather than research evidence. We conducted a cross-sectional online and postal survey among UK-based consultant gynaecologists and fertility specialists, to explore compliance with this guideline. A total of 110 responses met the inclusion criteria. During first-cycle treatment with clomifene, 50.9% of respondents were not always using TVUS, and 21.8% never were. Clinicians who did not have immediate access to TVUS were significantly less likely to scan (p < 0.01). Other key factors influencing practice were, personal experience of the clinician, lack of an evidence base to support the guideline and a willingness to accept the risk of multiple pregnancy. Several respondents questioned the value of scanning the first cycle only and highlighted that over-response may be seen in subsequent cycles. This study confirms that there is variation in adherence to the guideline and uncertainty about the clinical need for scan monitoring. Further evidence to support or refute the guideline is required.

Context: Gonadotropin-releasing hormone (GnRH) antagonists in fixed or flexible regimens are used for prevention of premature luteinizing hormone (LH) surge, however, data comparing these regimens in stimulated intrauterine insemination (IUI) cycles are lacking. Aims: The aim of this study is to evaluate the effectiveness of GnRH antagonists in fixed and flexible regimens on the rate of premature luteinization (PL) and ovulation rate in sequential clomiphene-gonadotropin controlled ovulation–IUI cycles. Settings and Design: This study was conducted at tertiary care center; this was randomized controlled study. Materials and Methods: A total of 45 infertile women randomized into three groups of 15 each received clomiphene citrate + human menopausal gonadotrophin. GnRH antagonist was added according to fixed (n = 15) and flexible (n = 15) protocol. No antagonist in control group (n = 15). PL was defined as LH level ≥10 mIU/ml and progesterone level ≥1.0 ng/ml. Statistical Analysis: Mean values compared using the Student's t-test or one-way analysis of variance. Categorical variables distribution tested using either Pearson's Chi-square or Fisher's exact test as appropriate. Results: Of a total of 45 women, 58% (n = 26) presented with primary and 42% (n = 19) secondary infertility with mean age of 30.8 ± 3.43 years and BMI 26.57 ± 3.22 kg/m2. Fixed regimen (3.7%) showed most reduction in PL compared to flexible (15.38%, P = 0.33) or control (36.67%, P = 0.004). On human chorionic gonadotropin day, mean LH (P = 0.002) and progesterone (P = 0.079) levels in fixed, flexible, and control groups were as follows: 5.04 ± 5.47 mIU/ml, 3.95 ± 4.16 mIU/ml, 9.57 ± 7.91 mIU/ml, and 0.409 ± 0.320 ng/ml, 0.579 ± 0.727 ng/ml, and 1.033 ± 1.022 ng/ml, respectively. Ovulation (P = 0.813) and pregnancy rates (P = 0.99) were 88.9%, 84.6%, and 90% and 22.2%, 19.23%, and 10% in fixed, flexible, and control groups, respectively. Conclusions: Addition of antagonist in any regimen appears to lower PL rates and improve pregnancy rates in controlled ovarian stimulation and IUI cycles.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. It is characterized by a combination of hyperandrogenism (either clinical or biochemical), chronic oligo/anovulation, and polycystic ovaries. It is frequently associated with insulin resistance and obesity. PCOS receives considerable attention because of its high prevalence and possible reproductive, metabolic, and cardiovascular consequences. It is the most common cause of anovulatory infertility. Ovulation induction with clomifene citrate is the first line medical treatment. The aim of ovulation induction is monofollicular growth to avoid multiple pregnancy. The second line treatments include gonadotrophins and laparoscopic ovarian drilling. The role and benefit of metformin in ovulation induction is controversial. Woman with PCOS undergoing IVF are at significant risk of ovarian hyperstimulation syndrome. Women with PCOS are also at an increased risk of developing gestational diabetes, pregnancy induced hypertension, and pre-eclampsia.

Aim . In the real research test with an antiestrogen clomifene is offered for differential diagnostics of potential reversibility of a hypogonadism. Material and method s. After initial determination of levels of testosterone and LH, to 55 men with a hypogonadism clomifene citrate of 50 mg orally daily in the morning for 10 days was administrated. Levels of testosterone and LH repeatedly were defined on the 11th day. Results . The carried-out test with clomifene eliminated a hypogonadism at 85,5% of patients, thus the effect remained at 40%. The test was safe, at one of men of side effects it wasn’t noted. For patients with negative result of test (preservation of a hypogonadism) administration of preparations of testosterone was recommended. Conclusions . Test allows not only to differentiate reversibility of a hypogonadism, but also in some cases completely to eliminate it.

Resume Une patiente souffrant de sterilite anovulatoire a suivi un traitement a base de clomifene. Celui-ci n’ayant pas donne les resultats escomptes, son medecin a choisi d’y associer des injections de gonadotrophine chorionique humaine.

Background: Infertility is the most common problem in recent times. Primary infertility is the main concern in infertile couples. Different groups of pharmacological agents are available in the market to induce ovulation. Aims and Objectives: The purpose of this retrospective analysis of cost variation in ovulation inducing agents is to compare the cost-analysis of various ovulation induction agents which are used in infertility patients. Materials and Methods: To review the price list of ovulation induction agents, the current index of medical stores April 2018 and online sources were used as an information guide. Results: The cost of 11 drugs were analyzed, which were manufactured by different pharmaceutical companies in different doses and formulations in Indian market. Table 1 shows the variation in price of parenteral ovulation induction agents. The cost variation is higher in human menopausal gonadotropin 150 IU (206.76), cetrorelix 0.25 mg (190.43) followed by chorionic gonadotropin 2000 IU (181.25). Table 2 shows the variation in price of oral ovulation induction agents. The cost variation is more in Letrozole 2.5 mg (6566.66) followed by clomifene 50 mg (217.65). Conclusion: There are ample differences in the cost of different brands of ovulation inducing agents available in India. All agents have significant role in the management of infertility. The clinicians prescribing these drugs should have awareness of these cost variations, so as to reduce the cost of drug therapy and increase patient adherence to the therapy.

INTRODUCTION: This study was undertaken to compare between clomiphene citrate (CC) and gonadotropin-releasing hormone antagonist-based protocols in donor-recipient cycles in terms of parameters of ovarian stimulation and obstetric outcome. MATERIALS AND METHODS: Two hundred and three fertile oocyte donors were stimulated using two different protocols: Clomiphene based (n = 103) and antagonist based (n = 100). Donors in the one group were stimulated from day 1 or 2 of spontaneous or withdrawal bleeds with CC (50 mg/day) and recombinant follicle-stimulating hormone (FSH) till the day of trigger while donors in the other group were stimulated using recombinant FSH from day 1 or 2, and the antagonist was added as per flexible antagonist protocol. When >3 follicles were >17 mm in diameter, trigger was given with 2 mg leuprolide intramuscular. Transvaginal oocyte retrieval was done after 34 h of trigger. RESULTS: There was no significant difference in between the two groups in terms of age, antral follicle count, starting dose of gonadotropins, total dose required, duration of stimulation, number of follicles retrieved, mature follicles, and fertilization rate. The serum estradiol levels were significantly raised in the clomiphene group (P < 0.001). Pregnancy rate was similar in both the groups. The clinical pregnancy rate was 65.94% in the clomiphene group and 57.46% in the antagonist group. The live birth rate per cycle started was 47.8% in the clomiphene group and 39.55% in the antagonist group. There was one case of ectopic pregnancy in the antagonist group. CONCLUSION: Controlled ovarian stimulation using clomiphene and gonadotropin is a viable option for donor oocyte cycles. The cost and number of injections used per cycle can be reduced by using the clomiphene-based protocols.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age and by far the most common cause of anovulatory infertility. Lifestyle change alone, and not in combination with pharmacological ovulation induction such as clomifene citrate or metformin, is generally considered the first-line treatment for the management of infertile anovulatory women with PCOS who are overweight or obese. Clomifene citrate should be considered as a first-line pharmacological therapy to improve fertility outcomes. Second-line medical treatments may include ovulation induction with gonadotropins (in clomifene citrate-resistant or clomifene citrate failure women) or laparoscopic ovarian drilling (in clomifene citrate-resistant women) or possibly with metformin combined with clomifene citrate (in clomifene citrate-resistant women). There is currently insufficient evidence to recommend aromatase inhibitors over that of clomifene citrate in infertile anovulatory women with PCOS in general or specifically in therapy-naive or clomifene citrate-resistant women with PCOS.

To observe the clinical efficacy of combined acupuncture and herbal formula for male sterility. Thirty-seven sterility cases due to abnormal semen were randomly allocated into two groups, a group of combined acupuncture and herbal formula (observation group, n=25) and a group of combined acupuncture and oral clomifene capsules (control group, n=12). Then the clinical symptoms, routine semen indexes, testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) changes have been observed in two groups respectively before and after treatment. Combined acupuncture and herbal formula obtained substantially better effect than combined acupuncture and oral Western medication (P

Polycystic ovary syndrome (PCOS), the most common endocrinopathy of reproductive-aged women, is characterized by ovulatory dysfunction and hyperandrogenism.The aim was to compare gene expression between endometrial samples of normal fertile controls and women with PCOS.We conducted a case control study at university teaching hospitals.Normal fertile controls and women with PCOS participated in the study.Endometrial samples were obtained from normal fertile controls and from women with PCOS, either induced to ovulate with clomiphene citrate or from a modeled secretory phase using daily administration of progesterone.Total RNA was isolated from samples and processed for array hybridization with Affymetrix HG U133 Plus 2 arrays. Data were analyzed using GeneSpring GX11 and Ingenuity Pathways Analysis. Selected gene expression differences were validated using RT-PCR and/or immunohistochemistry in separately obtained PCOS and normal endometrium.ANOVA analysis revealed 5160 significantly different genes among the three conditions. Of these, 466 were differentially regulated between fertile controls and PCOS. Progesterone-regulated genes, including mitogen-inducible gene 6 (MIG6), leukemia inhibitory factor (LIF), GRB2-associated binding protein 1 (GAB1), S100P, and claudin-4 were significantly lower in PCOS endometrium; whereas cell proliferation genes, such as Anillin and cyclin B1, were up-regulated.Differences in gene expression provide evidence of progesterone resistance in midsecretory PCOS endometrium, independent of clomiphene citrate and corresponding to the observed phenotypes of hyperplasia, cancer, and poor reproductive outcomes in this group of women.

Mild ovarian stimulation for in vitro fertilization usually refers to the use of low-dose gonadotropins in conjunction with a gonadotropin-releasing hormone (GnRH) antagonist whereas minimal stimulation refers to the use of a sequential administration of clomiphene citrate followed by low-dose gonadotropins and a GnRH antagonist. These protocols offer important cost and tolerability advantages to all patients but specifically to high and low responders.

To compare the clinical outcomes of letrozole and laparoscopic ovarian drilling (LOD) in patients with clomiphene-citrate-resistant polycystic ovary syndrome (PCOS).In the present prospective randomized trial, 140 women with clomiphene-citrate-resistant PCOS were randomly allocated to receive 5mg letrozole from day 3 to day 7 of menses for 6 consecutive cycles, or to undergo LOD. When a leading follicle of at least 18 mm was present, ovulation was triggered with human chorionic gonadotropin (hCG). The 6-month rates of ovulation, pregnancy, abortion, and live births were evaluated.The groups were similar with regard to baseline clinical characteristics and hormonal profiles. The ovulation rate was significantly higher in the letrozole group than in the LOD group (59.0% versus 47.5%). On the days of the hCG injection, women in the letrozole group had a significantly thicker endometrium than those in the LOD group (P0.0001). Women receiving letrozole had a higher pregnancy rate (35.7% versus 28.6%) and a lower rate of spontaneous abortion (8.0% versus 20.0%, respectively), but these differences were not statistically significant.Letrozole seems to be a suitable second-line ovulation-inducing alternative to LOD in women with PCOS who do not conceive with clomiphene citrate.

Objective To compare different methods of ovarian stimulation (OS) for assisted reproductive technology in baboons. Design Prospective randomized study. Setting Institute of primate research. Animal(s) Baboons (n = 10) were randomized into two groups (of five animals each) during three different cycles to compare six protocols of OS. Intervention(s) Cycle 1: clomiphene citrate (CC) alone (group CC) versus CC and GnRH agonist (group CC-Ag); cycle 2: recombinant gonadotropins (GON) without GnRH agonist (group GON) versus GON and depot GnRH agonist (group GON-AgDepo-1); cycle 3: GON and depot GnRH agonist (group GON-AgDepo-2) versus GON and daily GnRH agonist in a classic long protocol (group GON-Ag). Oocyte aspiration was performed 34–36 hours after injecting 5,000 IU rhCG, followed by fertilization via intracytoplasmic sperm injection (ICSI). Main Outcome Measure(s) Number and quality of oocytes retrieved and their fertilization rate. Result(s) More metaphase II (MII) oocytes were retrieved using the GON-AgDepo-1 (n = 12; 64% MII), GON-AgDepo-2 (n = 9; 79% MII), GON-Ag (n = 16; 88% MII), and GON (n = 6; 59% MII) protocols compared with the CC (n = 9; 15% MII) and CC-Ag (n = 14; 20% MII) protocols. Fertilization by ICSI varied between 43% and 71%. Conclusion(s) In baboons, long and depot protocols yield similar numbers of MII oocytes; however, depot protocol may be preferable because only one injection of GnRH agonist is needed.

Objective. To compare the efficacy of intrauterine insemination vs. timed intercourse with clomiphene citrate as a first-line treatment for anovulatory infertility associated with polycystic ovary syndrome. Design. A randomized controlled trial following the CONSORT criteria. Setting. A university hospital and a private practice setting. Patients. 188 women (525 cycles) with polycystic ovary syndrome. Main outcome measures. Women received three consecutive cycles of ovulation induction with clomiphene citrate and intrauterine insemination (n=93, 259 cycles) or three consecutive cycles of clomiphene citrate with timed intercourse (n=95, 266 cycles). Outcome measures. Clinical pregnancy rate per cycle, number of growing and mature follicles, serum estradiol, endometrial thickness at the hCG day, serum progesterone, ovulation, miscarriage and live birth rates. Results. There were no differences between the two groups regarding the clinical pregnancy rate per cycle or per woman (8.49 vs. 7.89% and 23.6 vs. 22.1%; p=0.26 and p=0.33, respectively). Two twin pregnancies occurred in each group. Miscarriage and live birth rates were comparable (18.1 vs. 19% and 19.35 vs. 17.89%; p=0.31 and p=0.33, respectively). No ectopic, higher-order pregnancies or cases of ovarian hyperstimulation syndrome occurred. No differences were found regarding the number of follicles, serum progesterone, ovulation rates, estradiol levels or endometrial thickness at the hCG day (7.7±0.4 vs. 7.5±0.6mm; p=0.54). Conclusions. Ovulation induction with clomiphene citrate and timed intercourse is as effective as that with intrauterine insemination for achieving pregnancy in polycystic ovary syndrome and could represent the initial treatment option, being less invasive and less expensive than intrauterine insemination.

Resume Objectif Mise au point sur les donnees de la litterature concernant l’induction de l’ovulation. Methodologie generale Les articles et etudes retenus pour l’elaboration de l’argumentaire des recommandations sur les indications et les bonnes pratiques des inducteurs de l’ovulation ont ete obtenus grâce a une recherche sur PubMed et Medline, Cochrane database a l’aide de plusieurs mots cles : « induction de l’ovulation, citrate de clomiphene, gonadotrophines, metformine, anti-aromatases, pompe a GnRH, cancer, hyperstimulation ovarienne, thromboses, grossesses multiples, complications… » parus jusqu’en 2010 inclus. Les articles retenus en priorite sont des etudes randomisees de grands effectifs, les dernieres meta-analyses parues, les etudes de cohortes et lorsque les donnees de litteratures etaient insuffisantes cela etait precise.

Clomifene citrate has long been used as a first-line ovulation induction agent for women wishing to conceive who have normogonadotropic anovulation (absent or irregular ovulation). Women who ovulate but do not conceive after several cycles with clomifene citrate are usually switched to ovulation induction with gonadotrophins, with or without intrauterine insemination. However, no randomized clinical trials have investigated the effectiveness of a switch to gonadotrophins and intrauterine insemination compared with continued treatment with clomifene citrate.TheModified Ovulation Induction (M-OVIN) study was a 2-by-2 factorial multicenter randomized clinical trial conducted in 48 Dutch hospitals between December 8, 2008, and December 16, 2015. The aim of the study was to determine whether switching to gonadotrophins is more effective than continuing clomifene citrate and whether addition of intrauterine insemination is more effective than intercourse. Subjects were women aged 18 years and older who had normogonadotropic anovulation and were not pregnant after 6 ovulatory cycles of clomifene citrate (maximum of 150 mg daily for 5 days). Using a central password-protected, Internet-based randomization program, women received one of the following: (1) 6 cycles with gonadotrophins plus intrauterine insemination, (2) 6 cycles with gonadotrophins plus intercourse, (3) 6 cycles with clomifene citrate plus intrauterine insemination, or (4) 6 cycles with clomifene citrate plus intercourse. Dosages of clomifene citrate varied from 50 to 150 mg daily orally and gonadotrophins were administered subcutaneously with a starting dose of 50 or 75 IU daily. The primary study outcome was conception leading to live birth within 8 months defined as any baby born alive with a gestational age of more than 24 weeks. Primary analysis was according to intention-to-treat. Two comparisons were made: gonadotrophins compared with clomifene citrate and intrauterine insemination compared with intercourse.A total of 666women were randomized: 166 to ovulation induction with gonadotrophins combined with intrauterine insemination, 165 to ovulation induction with gonadotrophins, 163 to ovulation induction with clomifene citrate combined with intrauterine insemination, and 172 to continued ovulation induction with clomifene citrate. Women receiving gonadotrophins had significantly more live births than women receiving clomifene citrate (52% [167/ 327] vs 41% [138/ 334]; the relative risk [RR] was 1.24, with a 95% confidence interval [CI] of 1.05 to 1.46; P = 0.0124). Adding intrauterine insemination did not increase live birth rates compared with intercourse (49% vs 43%; RR, 1.14; 95% CI, 0.97-1.35; P = 0.1152).Multiple pregnancy rates were low for the 2 comparisons and not different. Three adverse events were noted: 1 woman treated with clomifene citrate conceived a child with congenital abnormalities, 1 woman treated with gonadotrophins delivered at a gestational age of 20 weeks due to cervical insufficiency, and 1 woman treated with clomifene citrate had a stillbirth.These data show that for normogonadotropic anovulatory women with clomifene citrate failure, switching to gonadotrophins increases the live birth rate over continued treatment with clomifene citrate. There is no evidence that the addition of intrauterine insemination increases live birth rates. A randomized trial and network meta-analyses have reported that letrozole is associated with higher live birth rates than clomifene citrate. The authors suggest that future studies investigate whether letrozole is also effective and safe for women who have not conceived within the first 6 months of treatment.

The aerial parts of Coccinia cordifolia L. are used to treat female infertility in West Bengal state of India.The present study was undertaken to evaluate the fertility inducing effect of aerial parts of Coccinia cordifolia L. in female rats.The effect of aqueous extract of Coccinia cordifolia L. on hyperprolactinemia induced infertility, endometriosis induced infertility and androgen-induced infertility was studied. The effect on serum estrogen level, serum progesterone level and reproductive tract was also evaluated in normal healthy female rats. The extract was administered orally at two different doses of 500 mg/kg and 1000 mg/kg.In hyperprolactinemia induced infertility model, the numbers of uterine implants were almost 10 times more in the extract treated groups as compared to control. The high dose of extract also produced a significant increase in serum estrogen levels (p0.01) and number of corpus luteum (p0.05) in healthy female rats. The extract at both doses was effective in reducing the weight of endometrial implants by 70-80%, but failed to induce fertility in rats with endometriosis. The extract was ineffective in inducing fertility in androgen-induced infertility model.The aqueous extract of Coccinia cordifolia L. induces fertility in hyperprolactinemia induced infertility model in female rats.

Ovarian dysfunction is probably the pivotal feature of polycystic ovary syndrome (PCOS) making this syndrome a major cause of anovulatory infertility in developed countries. Several approaches have been proposed to induce ovulation in PCOS patients. Notwithstanding lifestyle modifications, clomiphene citrate, surgery and, finally, gonadotropins are the classical and still effective therapeutic options. New drugs, such as metformin and aromatase inhibitors are today available in the treatment of anovulation related to PCOS. The aim of the present review is to describe all therapeutic approaches to the anovulatory PCOS patients.

Objective To compare endocrine and follicular dynamics in ovulatory volunteer women in natural cycles and cycles stimulated with clomiphene (CC) and letrozole (LE). Design Prospective, randomized, double-blind, crossover study. Setting A private tertiary fertility center. Patient(s) Thirty ovulatory volunteer women ( Intervention(s) Randomized ovarian stimulation with CC and LE compared with no treatment. Main Outcome Measure(s) Hormone profiles, follicular development, and endometrial development through the cycles. Result(s) The LE-treated cycles had the shortest follicular phase (13.1 vs. 13.9 days with CC) with less multiple follicular development than CC. They showed higher midfollicular LH concentrations (7.5 IU/L vs. 6.0 IU/L), lower LH surge values (27.9 IU/L vs. 44.4 IU/L), and lower E 2 concentrations than natural cycles. The LE cycles showed significant increases in free androgen index in the midfollicular phase compared with the CC cycles. Endometrial thickness in LE cycles (8.3 mm) was similar to natural cycles, whereas in CC cycles it was reduced (7.6 mm vs. 8.5 mm) compared with natural cycles. Ovulation profiles were similar in all cycles. Conclusion(s) The LE treatment of normal women led to multiple follicular development, but less than CC. Estradiol concentrations were reduced, follicular phase length was shorter, whereas endometrial thickness and luteal P were normal. Follicular phase increased free androgen index is a novel finding and may explain the physiological observations.

Objective To compare the efficacy of clomiphene citrate (CC) plus tamoxifen with that of laparoscopic ovarian drilling in clomiphene-resistant women with polycystic ovary syndrome (PCOS). Method We randomly allocated 150 women with CC-resistant PCOS to a combined medication group (group 1) or a laparoscopic surgery group (group 2). The primary outcome was the live birth rate in each group; secondary outcomes were the rates of ovulation, clinical pregnancy and miscarriage. Results There were no significant differences between the groups regarding rates of ovulation (81.3% vs 85.3%), pregnancy (53.3% vs 50.7%), or live births (49.3% vs 44.0%), but the mean endometrium thickness was significantly greater on the day of human chorionic gonadotropin administration in group 1 (P Conclusion Clomiphene citrate plus tamoxifen was as effective as laparoscopic ovarian drilling in promoting ovulation and pregnancy.

Objective To compare the effects of anastrozole (1 mg) and clomiphene citrate (CC; 100 mg) used for ovulation induction in women with polycystic ovary syndrome. Design Prospective controlled trial. Setting University teaching hospital and private-practice setting. Patient(s) The study comprised a total of 216 infertile women (469 cycles) with polycystic ovary syndrome. Intervention(s) Patients received anastrozole (1 mg/d; 115 patients, 243 cycles) for 5 days, starting on day 3 of menses. A matched historical group of patients with polycystic ovary syndrome who were treated with CC (100 mg/d; 101 patients, 226 cycles) was used as a control group. Timed intercourse was advised 24–36 hours after hCG injection. Main Outcome Measure(s) Number of follicles, serum E 2 , serum P, endometrial thickness, and pregnancy and miscarriage rates. Result(s) The mean age, parity, and duration of infertility in both groups were similar, but statistically significantly more polycystic ovaries were found in the anastrozole group (odds ratio=2.44; 95% confidence interval=1.19–5.02). The total numbers of follicles were significantly higher in the CC group (3.8 ± 0.6 vs. 3.4 ± 0.5). Endometrial thickness at the time of hCG administration was significantly greater in the anastrozole group (10.1 ± 0.22 mm vs. 8.2 ± 0.69 mm). The duration of stimulation was similar in the two groups. Ovulation occurred in 165 (67.9%) of 243 cycles in the anastrozole group and in 150 (68.6%) of 226 cycles in the CC group without significant difference. Serum P was significantly higher in the CC group (7.1 ± 1.11 vs. 8.1 ± 0.88 ng/mL). The pregnancy and miscarriage rates were similar in the two groups. Conclusion(s) Anastrozole was associated with significantly fewer mature and growing follicles, thicker endometrium, and slightly higher pregnancy rate. Anastrozole may be helpful in situations in which multiple pregnancy is not desirable or the risk of ovarian hyperstimulation syndrome is high.

The interaction of clomifene citrate with nuclear fast red and sodium dodecyl benzene sulfonate (SDBS) was investigated by absorption and resonance rayleigh scattering (RRS) spectrometry. Clomifene citrate can react with nuclear fast red and sodium dodecyl benzene sulfonate to from a ternary complex, resulting in the enhancement of RRS intensity and the appearance of new RRS peaks. Based on that, a novel method is proposed for the determination of clomifene citrate by RRS technique. On the optimum conditions, there was good linearship between the increments of RRS intensity and the concentration of clomifene citrate in the range of 0.25 to 20.0 μg/mL, with the detection limit of 29 ng/mL. The proposed method was applied to assay the clomifene citrate tablets and capsules in agreement with the method in Chinese Pharmacopeia. In addition, the method was also applied to detect clomifene citrate in serum and urine samples with satisfactory results. The studies indicate that clomifene citrate acts as a bridge to band with nuclear fast red and SDBS by virtue of electrostatic attraction to form ion-association complexes.

This case illustrates some of the difficulties in treating anovulatory women with polycystic ovary syndrome, which is the most common cause of anovulatory infertility. Insulin resistance is a contributing factor to the pathogenesis of the syndrome. Assisted conception therapy is an effective treatment for women with polycystic ovary syndrome who are refractory to standard ovulation induction therapies or who have co-existing infertility factors. However, women with polycystic ovaries are particularly sensitive to stimulation with gonadotropins and have an increased risk of developing ovarian hyperstimulation syndrome. Background. A 25-year-old South Asian woman presented at an infertility unit with a 2-year history of anovulatory infertility. She had experienced irregular and infrequent periods for over a decade. Investigations. Endocrine profile (follicle-stimulating hormone, luteinizing hormone, thyroid-function test, prolactin, testosterone), oral glucose tolerance test and pelvic ultrasonography were performed. Diagnosis. Polycystic ovary syndrome, in accordance with the recent Rotterdam consensus (2004) criteria. Management. The patient failed to conceive by conventional ovulation-induction therapies with clomifene and gonadotropins. She subsequently underwent an in vitro fertilization cycle, to which she over-responded and developed a severe form of ovarian hyperstimulation syndrome. The diagnosis of ovarian hyperstimulation syndrome was based on clinical and ultrasonographic features. She was hospitalized and needed extensive supportive care, including insertion of chest and abdominal drains.

background: Anti-Mullerian hormone (AMH) has been implicated in the pathogenesis of polycystic ovary syndrome (PCOS). The aim of this study was to measure circulating AMH before laparoscopic ovarian diathermy (LOD) to evaluate its prognostic value for an ovulatory response and to investigate AMH changes after LOD to further explore the effects of LOD. methods: This prospective study included anovulatory women with PCOS undergoing LOD (n ¼ 29) or receiving clomiphene citrate (n ¼ 18). Plasma AMH concentrations were measured before and 1 week after treatment. Further measurements of AMH were made at 3- and 6-month follow-up. results: The pretreatment median (range) plasma AMH concentrations were 6.1 (1.0 -21.0) and 5.7 (1.3 -9.5) ng/ml in women having LOD and clomiphene citrate treatment, respectively. Women who ovulated after LOD (n ¼ 24) had a significantly (P ¼ 0.032) lower pre- operative AMH (5.6 (1.0- 21.0) ng/ml) compared with the non-responders (9.0 (6.1- 17.1) ng/ml). Using receiver-operating characteristic curve analysis, AMH was found to be a useful predictor of no ovulation after LOD with area under the curve of 0.804 (P ¼ 0.025). Using a cut-off of 7.7 ng/ml, AMH had a sensitivity of 78% and a specificity of 76% in the prediction of no ovulation after LOD. For all patients (n ¼ 47, clomiphene citrate or LOD), plasma AMH 7.7 ng/ml was associated with a reduced chance of ovulation after treatment (P ¼ 0.004). Following LOD, the median AMH concentration significantly (P ¼ 0.003) decreased to 4.7 (0.3 -15.1) ng/ml and remained low at 3- and 6-month follow-up. conclusions: Pretreatment circulating AMH level seems to be a good predictor of the ovarian response to LOD.

Although administration of Clomiphene Citrate (CC) is an effective therapy for ovulation induction in PCO patients, 15 to 20% of PCO patients do not ovulate following CC treatment. The aim of this study was to compare the endocrine dynamics (LH pulsatile pattern, FSH and steroid hormone changes) in 6 patients who ovulated (PCOS) and 6 PCO patients who did not ovulate in response to CC (PCOR). Blood was collected at 15 min intervals for 4 hr on day 9 of the first menstrual cycle (control cycle) and on day 9 of the following (treatment) cycle. In this cycle all women received 100 mg CC/day from day 5 to day 9. LH was determined in all samples whereas FSH and estradiol were measured every 60 min. No significant differences were observed regarding the age, body mass index, degree of hirsutism, ovarian volumes and basal levels of reproductive hormones between both groups of PCO women. During the control cycle, the LH pulse amplitude and transverse LH mean concentrations in PCOR patients were higher than in PCOR patients whereas the LH pulse frequency was similar in both groups. No difference was found in FSH and estradiol values between both groups. Compared to the control cycle, PCOR patients showed no change in the pulse amplitudes and no difference in LH, FSH and estradiol values following CC treatment. In contrast, during the CC therapy in PCOS patients an increase in the LH amplitude (p less than 0.05), the transverse mean LH concentration (p less than 0.05), FSH and estradiol was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

To clarify the significance of clomiphene test in spermatogenic disorders, it was performed on three groups of subjects: 10 with normozoospermia, 29 with oligozoospermia, and 11 with azoospermia. Two basal blood samples were drawn five days apart; prolactin, FSH, LH, estradiol, testosterone, androstenedione and sex-hormone-binding globulin were determined. 100 mg of clomiphene per day were administered for eleven consecutive days; another sample was drawn on the eleventh day and all the basal parameters, except prolactin, were determined. It may be concluded from the results: a) All the parameters studied increased significantly after clomiphene; and b) Testosterone levels obtained after clomiphene, as well as the increases in this hormone during the test and the ratio delta T/delta LH, were significantly lower in the oligozoospermic group. This finding suggests a decrease in the testicular androgenic function of this group.

ContextPersistence of hypogonadism is common in male patients with prolactinomas under dopamine agonist (DA) treatment. Conventional therapy with testosterone causes undesirable fluctuations in serum testosterone levels and inhibition of spermatogenesis.ObjectiveTo evaluate the use of clomiphene as a treatment for persistent hypogonadism in males with prolactinomas.DesignOpen label, single-arm, prospective trial.PatientsFourteen adult hypogonadal males (testosterone InterventionClomiphene (50 mg/day orally) for 12 weeks.MeasuresTestosterone, estradiol, LH, FSH, and prolactin were measured before and 10 days, 4, 8, and 12 weeks after clomiphene. Erectile function, sperm analysis, body composition, and metabolic profiles were evaluated before and after clomiphene.ResultsTen patients (71%), five hyperprolactinemic and two normoprolactinemic, responded to clomiphene (testosterone >300 ng/dl). Testosterone levels increased from 201±22 to 457±37 ng/dl, 436±52, and 440±47 ng/dl at 4, 8, and 12 weeks respectively (0.001

Objective To evaluate the outcome of long letrozole therapy for induction of ovulation in patients with clomiphene-resistant polycystic ovary syndrome (PCOS). Design Prospective randomized controlled study. Setting University teaching hospital and a private practice. Patient(s) The study comprised 218 patients with clomiphene-resistant PCOS. Intervention(s) Patients were randomly allocated to treatment with either long letrozole therapy (n = 108; 219 cycles) or short letrozole therapy (n = 110; 225 cycles). Main Outcome Measure(s) Number of growing and mature follicles, serum E 2 (pg/mL), serum P (ng/mL), endometrial thickness, occurrence of pregnancy and miscarriage. Result(s) The number of ovulating patients was greater in the long letrozole group (65.7% vs. 61.8%), but without statistical differences. The total numbersof follicles during stimulation was significantly greater in the long letrozole group (6.7 ± 0.3 vs. 3.9 ± 0.4). The numbers of follicles ≥14 mm and ≥18 mm were significantly greater in the long letrozole group. There was no significant difference in the pretreatment endometrial thickness or endometrial thickness at the time of hCG administration between the two groups. Pregnancy occurred in 28 of 225 cycles in the short group (12.4%) and 38 of 219 cycles (17.4%) in the long letrozole group, and the difference was statistically significant. Conclusion(s) The long letrozole protocol (10 days) can produce more mature follicles and subsequently more pregnancies than the short letrozole thrapy (5 days).

Objective To evaluate the effect of a short-course pretreatment with metformin on hyperandrogenism, insulin resistance, cervical scores, and pregnancy rates in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Methods Thirty-seven women with CC-resistant PCOS were randomly assigned to be pretreated with 500 mg of metformin or placebo 3 times per day for 2 cycles, and 100 mg of CC was given on days 5 through 9 of the second cycle in both groups. Luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrostendione sulfate (DHEAS), total testosterone (T), glucose, and insulin levels were measured at baseline and after the first cycle, as well as body mass index (BMI), cervical score, and pregnancy rate. Results After 1 cycle, BMI, total T level, and percentage of participants with insulin resistance were significantly decreased in the metformin group, without any significant decrease in LH, FSH, and DHEAS levels; and in the second cycle, CC treatment resulted in a higher ovulation rate and a thicker endometrium in the metformin group. The pregnancy rate and cervical scores were also higher in that group. Conclusion The short-course pretreatment with metformin decreased hyperandrogenism and insulin resistance and improved cervical sores, ovulation rate, and pregnancy rate among women with CC-resistant PCOS.

Objective To compare uterine and ovarian blood flow, measured by Doppler ultrasound, in the follicular phase of the menstrual cycle, in women who conceived to women who did not conceive during that cycle. Design A prospective study of 192 women looking at markers of ovarian reserve between August 2000 and September 2002. Setting A fertility clinic. Patient(s) A cross-section of women attending for fertility advice and treatment. Intervention(s) Each woman was monitored during a natural cycle and then during a clomiphene challenge cycle (100 mg clomiphene given for 5 days from days 3–7 of the cycle). Doppler ultrasound scans were performed on days 3 and 12 of the natural cycle and day 11 of the clomiphene challenge cycle. Main Outcome Measure(s) Cycles in which women conceived were compared with those in which women did not conceive to see whether there were differences in uteroovarian blood flow parameters as measured by Doppler ultrasound scan in the follicular phase of the cycle. Result(s) In the 15 natural conception cycles there was an increased uterine artery peak systolic velocity at day 12 compared with 131 natural nonconception cycles (in which there was an opportunity to conceive). There were no differences in any uteroovarian blood flow parameters at day 3, and no differences in ovarian blood flow parameters (dominant follicle blood flow, dominant follicle pulsatility index), endometrial thickness or pulsatility at day 12. No differences were seen in any blood flow parameters in 10 clomiphene conception cycles compared with 116 clomiphene nonconception cycles. Conclusion(s) In the late follicular phase of natural conception cycles there is an increased uterine artery peak systolic velocity compared with nonconception cycles. This was not seen in clomiphene cycles in which conception occurred. There is very little in the literature comparing natural or clomiphene conception with nonconception cycles.

Objective To compare the effect on follicular growth and endocrine parameters of follicular phase administration of anastrozole to healthy, normoovulatory women in doses of 1 or 5 mg, respectively, with the conventional dosing regimen for ovulation induction with clomiphene citrate (CC). Design Randomized, assessor-blinded, single-center, three-armed study. Setting University-affiliated, tertiary referral center. Patient(s) Thirty-two, normoovulatory, normogonadotropic women. Intervention(s) Administration of anastrozole 1 mg (group A1), anastrozole 5 mg (group A5), or CC 50 mg (group CC50) from cycle days 3 to 7. Main Outcome Measure(s) Number of follicles ≥15 mm and ≥10 mm on the day of the endogenous LH surge. Result(s) The mean number of follicles ≥15 mm on the day of LH surge was 1.4 ± 0.5, 1.0 ± 0.4, and 0.8 ± 0.4 in groups CC50, A1, and A5, respectively, which was statistically significant. Furthermore, a statistically significant difference between groups was found for the size of the growing follicular cohort (follicles ≥10 mm) on cycle days 8 and 10 and on the day of LH surge. The area under the curve (adjusted for baseline values on cycle day 3 and time frame of assessment) of follicular phase E 2 levels was significantly different among the groups that were compared (223.0 ± 97.5, 69.2 ± 40.0, and 83.4 ± 36.4 for groups CC50, A1, and A5, respectively). Conclusion(s) CC 50 mg exerts a stronger stimulatory effect on follicular growth compared with anastrozole in doses of 1 or 5 mg. Anastrozole administration results in lower follicular phase E 2 levels.

30 oligozoospermia patients from the andrologic outpatient service of the University-Hospital for Gynecology and Obstetrics, Graz, Austria, received a treatment with clomiphene-citrate. A doses of 25 mg daily was given for 25 days, followed by a break of 5 days. This treatment cycle was repeated three times, providing a total of 4 months of therapy. Rigid criteria of selection were applied for the patients in this trial, pretreatment serum levels of FSH, LH, testosterone, prolactin and estradiol had to be in normal or low-normal range. After treatment FSH, LH and testosterone were re-evaluated and a semen analysis was performed. Six to eight weeks afterwards another spermiogram was done. A significant raise of sperm density was observed immediately after treatment and at the control 6-8 weeks after therapy. Motility and morphologic quality remained unchanged after the therapeutic course. Fructose content of seminal plasma raised significantly 6-8 weeks after therapy. FSH, LH and testosterone increased also on a significant level. 6 pregnancies could be achieved, no negative side effects of treatment had to be registered.

The effect of clomiphene citrate during sulpiride-induced hyperprolactinemia on pituitary function was tested in 8 healthy men, who ingested 100 mg of clomiphene, 150 mg of sulpiride or 100 mg of clomiphene + 150 mg of sulpiride daily for 7 days. Clomiphene treatment increased FSH and LH plasma concentrations and this increase was unaffected by sulpiride-induced hyperprolactinemia. Sulpiride intake alone did not alter serum gonadotropin concentrations. A reduced LH response to LHRH during sulpiride intake was seen, whereas the FSH response was unchanged. The prolactin response to TRH was unaffected during the combined sulpiride + clomiphene ingestion. Sulpiride treatment did not change the basal and/or clomiphene-stimulated gonadotropin secretion in healthy men. Thus, oligozoospermic men using psychotropic drugs and/or with hyperprolactinemia may be suitable candidates for clomiphene treatment.

Objective To investigate the relationship between the plasma concentrations of clomiphene citrate (CC) isomers zu- (Zu) and enclomiphene (En), and ovulation outcome. Design Prospective, cohort study. Setting Reproductive medicine and fertility center in a university teaching hospital, United Kingdom. Patient(s) Forty-two women with World Health Organization type 2 infertility. Intervention(s) 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). Main Outcome Measure(s) Ovulation. Result(s) 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. Conclusion 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.