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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.