Familial Mediterranean Fever (FMF), Female and Male Fertility: Literature Review

Семейная средиземноморская лихорадка (CCЛ) - моногенное наследственное аутовоспалительное заболевание, характеризующееся периодически повторяющимися приступами лихорадки, серозитами разной локализации, артритами, эризипелоидоподобным высыпанием. Хотя ССЛ болеют преимущественно представители популяций восточно-средиземноморского происхождения (турки, армяне, арабы, евреи-сефарды), в наши дни болезнь регистрируется по всему миру, что связано с непрерывными миграционными процессами. Потенциальные осложнения ССЛ (фиброз и амилоидоз) и их лечение колхицином могут повлиять на репродуктивную систему больных либо путем обструкции маточных труб, либо через избыточное образование дефектных сперматозоидов и ооцитов, либо вследствие овариальной/тестикулярной недостаточности. Амилоидоз с преимущественным отложением амилоида в яичниках и яичках может приводить к женскому и мужскому бесплодию. У мужчин колхицин в редких случаях индуцирует олиго/азооспермию. У женщин основными причинами бесплодия в прошлом считались дисовуляция и перитонеальная адгезия. В последние годы ситуация с фертильностью значительно улучшилась благодаря применению колхицина. В обзоре обобщается текущая информация о взаимосвязи женской и мужской фертильности с ССЛ и приемом колхицина; излагаются современные подходы к восстановлению репродуктивной функции при бесплодии. Акцент сделан на аспектах безопасности терапии, основные положения которой представлены в клинических рекомендациях по лечению ССЛ Европейской антиревматической лиги (EULAR,2016). Familial Mediterranean fever (FMF) is a monogenic inherited autoinflammatory disease characterized by recurrent episodes (attacks) of fever, serositis of different localization, arthritis, erysipelaslike rashes. Eastern Mediterranean persons (especially Turks, Armenians, Arabs, Sephardic Jews) are most frequently affected. Nowadays the disease is registered throughout the world because of migration processes. Potential complications of FMF (fibrosis and amyloidosis) and their treatment with colchicine may affect the reproductive system either by salpinx obstruction causing mechanical infertility, or by excessive formation of defective sperm and oocytes, either due to ovarian /testicular insufficiency. Amyloidosis can lead to female and male infertility with amyloid preponderance in the ovaries and testicles. Colchicine rarely induces oligo/ azoospermia in men. In women, disovulation and peritoneal adhesion were the main causes of infertility in the past. In recent years, the fertility situation has improved considerably due to the use of colchicine. The review summarizes current information on the relationship between female and male fertility with FMF and colchicine; modern approaches to restoring reproductive function in infertility are outlined. The focus is on the aspects of the safety of therapy, the main provisions of which are presented in the clinical recommendations for treatment of the FMF of the European Anti-Rheumatic League (EULAR, 2016).

Hormonal status of adolescents with varicocele

Varicocele is most frequently diagnosed in children and adolescents. Therefore, the assessment of the reproductive health of adolescents is highly relevant. Changes in the testicle with varicocele can trigger the development of hypogonadism, which, being masked by active puberty and not being corrected in time, may lead to infertility. Objective. Тo assess the changes in hormonal status of adolescents with left-sided varicocele, as well as the severity of testicular insufficiency depending on varicocele grade and time since surgery. Patients and methods. Adolescents with left-sided varicocele and adolescents without varicocele were annually tested for their serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol between the age of 14 and 17 years. We compared hormone levels and their dynamics between the experimental and control groups, between patients with different grades of varicocele, and between the same patients before/after surgery for varicocele. Results. Adolescents with varicocele often demonstrated changes in their hormonal status, including decreased levels of FSH, LH, and testosterone. More significant changes were observed in patients with grade III varicocele. Early varicocelectomy facilitated normalization of hormonal status in puberty. Key words: adolescents, varicocele, hormones

Oncofertility in men cured of Hodgkin’s lymphoma as a child

Hodgkin’s lymphoma, being a highly malignant disease, has now acquired the property of a curative one. The article describes the basic principles of therapy of children with Hodgkin’s lymphoma, slow fixation of risk-adapted treatment positions. The possibility of complete cure of most patients appeared, which made this tumor a unique model for studying the remote consequences of cancer treatment. After the antitumor treatment of Hodgkin’s lymphoma, boys may suffer from testicular insufficiency (due to cytostatics), obstructive azoospermia (as a consequence of radiation therapy in the pelvic area), hypogonadism (secondary - after exposure of the pituitary gland to radiation, primary - after exposure of the pelvis due to the toxic effects of cytostatics). In order to reduce the gonadotoxicity of treatment, studies are being conducted to modify chemotherapy in the direction of lowering the doses of alkylating cytostatics, reducing the doses of radiation therapy without losing the effectiveness of treatment. Regardless of the cause of male infertility diagnosis includes the collection of reproductive history, external examination of the genitals, analysis of ejaculate, ultrasound examination of the scrotum, assessment of hormone levels (follicle stimulating hormone, total testosterone, serum testosterone, luteinizing hormone, prolactin, inhibin B, thyroid stimulating hormone).

Noonan syndrome males display Sertoli cell-specific primary testicular insufficiency

Context Abnormalities in the hypothalamo–pituitary–gonadal axis have long been reported in Noonan syndrome (NS) males with only few data available in prepubertal children. Objective The aim of this study was to describe the gonadal function of NS males from childhood to adulthood. Design It is a retrospective chart review. Patients and methods A total of 37 males with a genetically confirmed diagnosis of NS were included. Clinical and genetic features, as well as serum hormone levels (LH, FSH, testosterone, anti-Müllerian hormone (AMH), and inhibin B) were analysed. Results Of the 37 patients, 16 (43%) children had entered puberty at a median age of 13.5 years (range: 11.4–15.0 years); age at pubertal onset was negatively correlated with BMI SDS (r = −0.541; P = 0.022). In pubertal boys, testosterone levels were normal suggesting a normal Leydig cell function. In contrast, NS patients had significant lower levels of AMH (mean SDS: −0.6 ± 1.1; P = 0.003) and inhibin B (mean SDS: −1.1 ± 1.2; P < 0.001) compared with the general population, suggesting a Sertoli cell dysfunction. Lower AMH and inhibin B levels were found in NS-PTPN11 patients, whereas these markers did not differ from healthy children in SOS1 patients. No difference was found between cryptorchid and non-cryptorchid patients for AMH and inhibin B levels (P = 0.43 and 0.62 respectively). Four NS-PTPN11 patients had a severe primary hypogonadism with azoospermia/cryptozoospermia. Conclusions NS males display Sertoli cell-specific primary testicular insufficiency, whereas Leydig cell function seems to be unaffected.

Infertility

The assessment of men with fertility problems is described in this chapter. The main causes of male infertility are testicular insufficiency due to congenital and acquired causes, obstructions of the male genital tract, genetic and endocrine abnormalities, urogenital infections, and varicoceles. Lifestyle can also have a negative influence on semen quality: smoking, obesity, drugs, and anabolic steroids influence sperm parameters and may reduce natural conception. Some chronic diseases also have a negative influence on fertility. History taking and physical examination should focus on prevalent causes of male infertility. Many decisions on diagnosis and treatment of male infertility are based on a semen analysis. It is therefore essential that the investigation is performed according to the recommendations of the world health organization manual for semen analysis.

The state of the reproductive and somatic cells of the testicles with primary hypogonadism in men

The course of male hypogonadism is analyzed in the dynamic functional system including gametogenesis and the endocrine hypothalamo-pituitary-gonadal cycle. Gametogenesis was assessed by the results of cytomorphological analysis of the ejaculate. The hypothalamo-pituitary-gonadal cycle was assessed by measuring FSH, LH, testosterone, and prolactin in the blood. A total of 343 men were examined, 314 of these with spermatogenesis disorders. The continuity of changes in the gametogenesis hypothalamopituitary-gonadal cycle system in the pathogenesis of hypogonadal and primary testicular insufficiency is determined.