The role of leptin in human reproduction

The article reviews the current literature about leptin, a hormone produced mainly in the adipose tissue, in terms of its role in reproduction. The structure of leptin, its biological activity as well as its influence on secretion of their hormones has been discussed. The leptin concentrations during the ovulatory cycle, pregnancy puerperium and assisted reproduction have been presented. It has been suggested that leptin may have an advantageous effect not only on oocyte and zygote development in the early stages, but also on the process of implantation and therefore its evaluation may be useful for the clinical determination of embryo quality in IVF-ET program.     

The role of the leptin in reproduction

PURPOSE OF REVIEW: Since its discovery in 1994, leptin has appeared to be a pleiotrophic hormone, governing energy homeostasis and affecting many tissues in the body. Numerous pieces of evidence have accumulated showing that leptin potentially plays an important role in the control of the reproductive function. RECENT FINDINGS: This review presents the major concepts for the role of leptin in the modulation of reproductive function. As a marker of the nutritional status, leptin affects the hypothalamo-pituitary-gonadal axis, regulating gonadotrophin-releasing hormone and luteinising hormone secretion, and appears to be a permissive factor in the onset of the puberty. This protein and its receptor have been found in the reproductive tissues, indicating that this system could be also implicated in several processes such as embryo development, implantation and pregnancy. Moreover, disorders of the leptin system have been related to some reproductive pathologies such as pre-eclampsia and polycystic ovary syndrome. However, controversy surrounds several aspects of the action of leptin in reproduction that require a deeper investigation of this system. SUMMARY: Results to date suggest that this system could be implicated in important reproductive processes such as embryonic development and implantation. Moreover, understanding the role of leptin might be useful for new treatments in reproductive pathologies.     

The role of leptin in breast cancer

Leptin, the protein hormone produced mainly by adipocytes, placenta and mammary epithelium plays a significant role in, e.g., control of metabolism, reproductive processes, immune processes, angiogenesis, haemopoiesis and oxidation of lipids. Since some authors link leptin to mechanisms of mammary cancer development, the clinical data has been screened to allow evaluation of the hypothesis.     

The role of myomectomy in fertility enhancement

PURPOSE OF REVIEW: To review current available literature on the relationship between fibroids and infertility with particular emphasis on the benefits of myomectomy. Pregnancy complications related to the presence of these lesions and to their removal are also addressed. RECENT FINDINGS: There is a biological plausibility supporting a causal relationship between fibroids and infertility. From a clinical point of view, this association is mostly supported by studies comparing pregnancy rate following IVF in women with and without fibroids. The emerging view is that submucosal, intramural and subserosal fibroids interfere with fertility in decreasing order of importance. There is one randomized controlled trial supporting the benefits of myomectomy in infertile women with fibroids. The beneficial effects of surgery are further supported by insights from clinical series showing that the pregnancy rate following myomectomy is satisfactory and by the strong benefits documented in the few nonrandomized comparative studies. An increased rate of obstetric complications has been reported in women carrying fibroids. Data regarding the course of pregnancy in operated women are scanty. The most significant (although rare) complication is rupture of the uterus during pregnancy or labour. SUMMARY: At present, owing to the lack of adequately designed trials aimed to clearly establish that lesions benefit from surgery, a comprehensive and personalized approach should be adopted. The most important variables to be considered are the age of the woman, the characteristics of the fibroids, the concomitant presence of fibroids-related symptoms and the presence of other causes of infertility.     

The role of fertility preservation in patients with endometriosis

Patients affected with severe endometriosis are at significant risk for ovarian tissue damage, which may lead to infertility, reduced response to ovarian stimulation, and occasionally, premature ovarian failure. The risk for a compromised ovarian reserve in young patients is especially high following repeated surgical intervention and in the presence of bilateral endometriomas. In many cases, enhanced loss of ovarian reserve may also result from the damaging effect of the pathologic process on follicle reservoir even without surgical interventions. Women diagnosed with severe endometriosis and those designated for extensive ovarian surgical intervention are frequently not planning to conceive. In light of recent advances in fertility preservation techniques (FPT), such as oocytes and ovarian tissue freezing, as well as their increasing success rates, we critically evaluate the options for FPT in patients suffering from endometriosis. Personalized counseling should be offered to all patients with endometriosis taking into account age, extent of ovarian involvement, current ovarian reserve, previous and impending surgeries for endometriosis, along with current success rates and possible risks associated with FPT.     

Gender differences in leptin levels and physiology: a role for leptin in human reproduction

Leptin, an adipocyte-derived hormone known to play an important role in body-weight regulation, has been shown to be expressed differentially in men and women. These observations are potentially important for the understanding of differences between men and women in regulation of food intake, weight gain, and body fat distribution. Leptin is also involved in female fertility, especially in pubertal development. It may well be the triggering signal for the onset of puberty in girls. Although the exact mechanisms and interactions with sex steroids are not yet fully established, it is clear that leptin plays a role as an endocrine mediator in sexual development and reproduction.     

In-vitro maturation: its role in fertility treatment

PURPOSE OF REVIEW: In-vitro maturation of oocytes was primarily developed to make in-vitro fertilization safer and simpler for women with polycystic ovaries and high risk of ovarian hyperstimulation syndrome. In-vitro maturation has potentially many advantages over conventional in-vitro fertilization. A simple protocol with decreased or no hormonal stimulation before oocyte retrieval and thus lower cost of the treatment cycle are clear benefits. More importantly, the risk of ovarian hyperstimulation syndrome is entirely avoided. RECENT FINDINGS: The clinical outcome has substantially improved in recent years with pregnancy rates between 20 and 54%. The birth of approximately 400 children has been reported in the literature, but about three times as many are known to have been born. The postnatal follow-up studies of the children have been reassuring. SUMMARY: Although good results have been reported by some clinics, in-vitro maturation has not yet become a mainstream fertility treatment. The most important reason for this is the lower chance of a live birth per treatment compared with conventional in-vitro fertilization. Several aspects of the clinical in-vitro maturation need to be improved to give in-vitro maturation a place among assisted reproduction techniques it deserves.     

The role of leptin in fetal growth: a short review from conception to delivery

Abnormally high- or low-serum maternal levels and/or levels in placental, umbilical blood, and fetus/neonate are associated with a wide spectrum of complicated pregnancies. Whereas the state of knowledge about mechanisms and pathways involving secondary or tertiary modulators is far from complete, the role of leptin from ovulation and implantation and throughout pregnancy underscores its importance in normal and abnormal states.     

Differential fertility by intelligence. The role of birth planning (Author's transl)

A survey was conducted in 1974 among white residents of 16 U.S. cities to investigate the relationship between intelligence and fertility. The IQ was measured with the Peabody Picture Vocabulary Test, and fertility was measured on the number of born children. Age, duration of marriage, profession, and influence of social milieu were also taken into consideration. An inverse relationship was found between fertility and IQ, caused by the fact that low IQ women had more unwanted births than high IQ women. It was also shown that low IQ women had an elevated failure rate with any contraceptive method, and that the best way to control their fertility was to utilize exclusively permanent contraceptive methods administered by a physician.     

The kinetics of leptin in Meigs' syndrome

OBJECTIVE: The aim of this study was to assess the kinetics and possible role of leptin in the pathophysiology of Meigs' syndrome. METHODS: We report on a 62-year-old patient admitted for a large ovarian tumor, hydrothorax, and ascites. The patient underwent abdominal hysterectomy and bilateral adnexectomy revealing a benign ovarian fibroma and no evidence of malignant cells in the pleural or peritoneal fluids. Analysis of serum, peritoneal, and pleural fluids from this patient was performed before, during, and after the operation. RESULTS: Preoperatively, the patient had low levels of leptin in the serum, peritoneal, and pleural fluids. Serum levels increased after removal of the ovarian tumor along with the resolution of ascites and hydrothorax. CONCLUSION: Leptin levels inversely correlate to tumor burden, third space fluid accumulation, and clinical status in Meigs' syndrome. These findings suggest the involvement of leptin in the pathophysiology of this syndrome.     

Research on fertility regulation has a key role in reproductive health

It is estimated that half of all pregnancies are unplanned. In many developing countries, at least half of all married women say they do not want any more children. In almost every African country, at least half of all married women want either to postpone their next pregnancy or do not want any more children. However, most of these women do not use any form of contraception. Since one of the key objectives of reproductive health care is to enable and support people to make responsible, voluntary decisions about child bearing and methods of family planning of their choice, and in view of the failure mentioned above to do so, increased support for biomedical, social science and operational research on fertility regulation is necessary. Reproductive health for all cannot be achieved unless all couples have means that are affordable and acceptable to them to regulate their own fertility. The range of choices available to men is especially limited. This issue of "Progress in Human Reproduction Research" reports on research conducted by the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction to increase the fertility regulation choices for women and men, and to evaluate the safety of existing methods. One article reports on a hormonal contraceptive for men; another confirms the lack of association between long-term DMPA use and cancer; and one reports on the acceptability of male hormonal methods currently under development.     

The function of the cervix in fertility

Recent advances and new findings relative to the role of cervix in fertility are reported in this review. Cervical mucus, which may include small amounts of endometrial, tubal, and possibly, follicular secretions, is produced at a rate of 20-60 mg/day in normal reproductive age women. This rate increases up to 700 mg/day during the immediate preovulation phase. To examine the physical properties of the cervical factor, assessments should include determination of amount, viscosity, ferning, spinnbarkeit, cellularity, pH, and cultural studies, if infection is suspected. The clinical evaluation of cervical mucus properties requires evaluation of the quality of the mucus, its functional ability, and its interaction with sperm, since it now appears that sperm are stored in the cervix and are released continuously to the upper part of the reproductive tract; in addition, present evidence indicates that cervical mucus acts as a barrier or trap for sluggish and abnormal sperms. In terms of infertility assessments, postcoital tests are the most useful, and if an adequate number of motile sperm are present in the endocervix, favorable cervical factor is assumed and mucus can be ruled out as the cause of infertility.     

分泌期子宫内膜瘦素和瘦素受体的表达

目的 探讨瘦素和瘦素受体系统在孕卵着床和种植过程中的作用。方法 应用免疫组化的方法检测36例分泌期子宫内膜石蜡标本中瘦素和瘦素长受体的表达。结果 瘦素在分泌期子宫内膜腺体和间质中呈阳性或强阳性表达,瘦素长受体在分泌期子宫内膜间质中呈弱阳性或阴性表达,瘦素长受体在分泌期子宫内膜腺体呈阳性或强阳性表达。结论 瘦素和瘦素受体系统在分泌期子宫内膜的研究,可能说明在孕卵着床和种植过程中发挥重要作用。     

The position of the fertility counsellor in a fertility team: A critical appraisal

The ongoing evolution of reproductive medicine has revealed the complexity of emotional reactions of couples seeking to fulfil their desire for a child. The position of counselling is evaluated from three perspectives: the couple, medical staff and the individual counsellor. This leads to three proposed levels of counselling, as an integrated component of Assisted Reproductive Technology (ART).     

The position of the fertility counsellor in a fertility team: a critical appraisal

The ongoing evolution of reproductive medicine has revealed the complexity of emotional reactions of couples seeking to fulfil their desire for a child. The position of counselling is evaluated from three perspectives: the couple, medical staff and the individual counsellor. This leads to three proposed levels of counselling, as an integrated component of Assisted Reproductive Technology (ART).     

The significance of leptin for reproduction

Leptin is mainly synthesized by adipocytes and might represent the connecting link between fatty tissue and brain. In reference to reproduction, leptin resistance could play a role particularly in the pathogenesis of the PCO syndrome. However, there exists at present contradictory data on this, so that further clarification is necessary. Leptin interacts with the steroid synthesis to a degree not yet precisely clarified and possesses receptors in numerous tissues, which suggests extensive local and endocrine effects. Its exact significance for the initiation of puberty still remains unknown. The same is true for first data regarding leptin and endometriosis and the interpretation of hyperleptinemia during pregnancy. It is clear that this protein mediates between fatty tissue and the reproductive function. However, the detailed physiologic and pathophysiologic role of leptin in reproduction can only be clarified through further extensive studies. To date there is not yet a practical importance for the measurement of leptin in routine work in reproductive medicine.     

The known and unknown of leptin in pregnancy

Leptin, which was identified originally as an adipocyte-derived protein, was regarded for years as an exclusive regulator of satiety and energy homeostasis. A role for leptin in pregnancy was later suggested by the findings that plasma levels during gestation are greater than in nongravid individuals and that leptin is synthesized within the fetoplacental unit. Observational studies have established that leptin production is dysregulated in several pathologic stages of pregnancy in association with alterations of fetal growth. For example, an overproduction of leptin by the placenta in pregnancy with diabetes mellitus or hypertension is associated with maternal hyperleptinemia. Evidence is also accumulating that umbilical leptin levels can be viewed as a biomarker of fetal adiposity. Ten years after its discovery as a hormone, we review the known and unknowns of leptin in pregnancy with particular emphasis on its functions in health and disease. We aim to demonstrate that studies of leptin in pregnancy largely have contributed to insight into the mechanisms of leptin action, both as a hormone and as a cytokine.