Annibale Volpe

Anti-Müllerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART)

BACKGROUND In women, anti-Müllerian hormone (AMH) levels may represent the ovarian follicular pool and could be a useful marker of ovarian reserve. The clinical application of AMH measurement has been proposed in the prediction of quantitative and qualitative aspects in assisted reproductive technologies (ART). In men AMH is secreted in both the serum and seminal fluid. Its measurement may be useful in clinical evaluation of the infertile male. METHODS The PubMed database was systematically searched for studies published until the end of January 2009, search criteria relevant to AMH, ovarian reserve, ovarian response to gonadotrophin stimulation, spermatogenesis and azoospermia were used. RESULTS AMH seems to be a better marker in predicting ovarian response to controlled ovarian stimulation than age of the patient, FSH, estradiol and inhibin B. A similar performance for AMH and antral follicular count has been reported. In clinical practice, AMH measurement may be useful in the prediction of poor response and cycle cancellation and also of hyper-response and ovarian hyperstimulation syndrome. In the male, the wide overlap of AMH values between controls and infertile men precludes this hormone from being a useful marker of spermatogenesis. CONCLUSIONS As AMH may permit the identification of both the extremes of ovarian stimulation, a possible role for its measurement may be in the individualization of treatment strategies in order to reduce the clinical risk of ART along with optimized treatment burden. It is fundamental to clarify the cost/benefit of its use in ovarian reserve testing. Regarding the role of AMH in the evaluation of infertile men, AMH as single marker of spermatogenesis does not seem to reach a satisfactory clinical utility.

Anti-Müllerian hormone (AMH): what do we still need to know?

In the ovary, Anti-Müllerian hormone (AMH) is produced by the granulosa cells of early developing follicles and inhibits the transition from the primordial to the primary follicular stage. AMH levels can be measured in serum and have been shown to be proportional to the number of small antral follicles. In women serum AMH levels decrease with age and are undetectable in the post-menopausal period. In patients with premature ovarian failure AMH is undetectable or greatly reduced depending of the number of antral follicles in the ovaries. In contrast, AMH levels have been shown to be increased in women with polycystic ovary syndrome (PCOS). AMH levels appear to represent the quantity of the ovarian follicle pool and may become a useful marker of ovarian reserve. AMH measurement could also be useful in the prediction of the extremes of ovarian response to gonadotrophin stimulation for in vitro fertilization, namely poor- and hyper-response. Although AMH has the potential to increase our understanding of ovarian pathophysiology, and to guide clinical management in a broad range of conditions, a number of important questions relating to both the basic physiology of AMH and its clinical implications need to be answered.

Vitrification versus controlled-rate freezing in cryopreservation of human ovarian tissue

BACKGROUND Controlled-rate freezing of ovarian cortical tissue for preservation of fertility among young women facing chemo- or radio-therapy is a widely accepted procedure. To improve the method for cryopreservation of ovarian tissue, particularly the stroma, we carried out a systematic comparison of vitrification versus slow programmed freezing. METHODS Ovarian tissue from 20 women, donated during Caesarean section, was used for parallel comparison of survival and detailed light and electron microscopic (EM) morphology of oocytes, granulosa cells and ovarian stroma after freezing (slow freezing and vitrification), thawing and 24-h culture. Using tissue obtained from the same patient, we compared four cryopreservation protocols and fresh tissue. The cryoprotectants used in slow freezing were 1,2-propanediol (PrOH)-sucrose and ethylene glycol (EG)-sucrose. For vitrification, tissues were incubated for 5 or 10 min in three solutions containing a combination of dimethyl sulphoxide (DMSO), PrOH, EG and polyvinylpyrrolidone (PVP). RESULTS Cryopreservation using controlled-rate freezing and vitrification preserved the morphological characteristics of ovarian tissue generally well. As revealed by morphological analysis, particularly EM, the ovarian stroma was significantly better preserved after vitrification than after slow freezing (P < 0.001). The follicles were similarly preserved after all freezing methods. CONCLUSIONS Vitrification using a combination of PrOH, EG, DMSO and PVP was comparable to slow freezing in terms of preserving follicles in human ovarian tissue. Ovarian stroma had significantly better morphological integrity after vitrification than after controlled-rate freezing.

Anti-Müllerian hormone (AMH) in female reproduction: is measurement of circulating AMH a useful tool?

Anti‐Müllerian hormone (AMH) is a dimeric glycoprotein, a member of the transforming growth factor (TGF) superfamily. It is produced exclusively in the gonads and is involved in the regulation of follicular growth and development. In the ovary AMH is produced by the granulosa cells of early developing follicles and seems to be able to inhibit the initiation of primordial follicle growth and FSH‐induced follicle growth. As AMH is largely expressed throughout folliculogenesis, from the primary follicular stage towards the antral stage, serum levels of AMH may represent both the quantity and quality of the ovarian follicle pool. Compared to other ovarian tests, AMH seems to be the best marker reflecting the decline of reproductive age. AMH measurement could be useful in the prediction of the menopausal transition. It could also be used to predict poor ovarian response and possibly the prognosis of in vitro fertilization (IVF) cycles. AMH has been shown to be a good surrogate marker for polycystic ovary syndrome (PCOS). Finally, its use as a marker for granulosa cell tumours has been proposed. A clearer understanding of its role in ovarian physiology may help clinicians to find a role for AMH measurement in the field of reproductive medicine.

An increased vulnerability to stress is associated with a poor outcome of in vitro fertilization-embryo transfer treatment

OBJECTIVE To evaluate the association between the vulnerability to stress and the treatment outcome of couples undergoing IVF-ET. DESIGN Controlled, prospective clinical study. SETTING The Assisted Reproduction Unit of the Department of Obstetrics and Gynecology, University of Modena. PATIENT(S) Forty-nine infertile women consecutively admitted to standard superovulation treatment. Mean age was 33.9 years, duration of infertility was 6.3 years. Reasons for assisted reproduction were mechanical factor in 22 cases, sperm problem in 9 cases, and endocrine disorder in 6 cases. In 12 cases, infertility was unexplained. More than 55% already had an IVF-ET attempt. INTERVENTION(S) The day of oocyte pick-up, subjects were submitted to Stroop Color and Word test, a task measuring the ability to cope with a cognitive stressor, involving attentional and sympathoadrenal systems. Systolic (SBP) and diastolic blood pressure, as well as heart rate (HR) were measured at baseline, during the test, and 10 minutes after the end of testing. MAIN OUTCOME MEASURE(S) The evidence of a biochemical pregnancy (beta-hCG value 12 days after ET) define the success and failure groups. RESULT(S) Sixteen women (33%) had a biochemical pregnancy, 12 also had ultrasound evidence. Eight gave birth to healthy infants. Age, education, causes, and duration of infertility were similar in the success and failure groups. The latter were more involved in a job outside home than the former. Moreover, they had a lower number of both fertilized oocytes and transferred embryos. In response to the Stroop test, every subject reported an increase of cardiovascular parameters. However, women becoming pregnant showed a lower response of both SBP and HR than women who failed. CONCLUSION(S) Both a major cardiovascular vulnerability to stress and working outside home are associated to a poor outcome of IVF-ET treatment.

Homeostatic versus Circadian Effects of Melatonin on Core Body Temperature in Humans

Evidence obtained in animals has suggested a link of the pineal gland and its hormone melatonin with the regulation of core body temperature (CBT). Depending on the species considered, melatonin intervenes in generating seasonal rhythms of daily torpor and hibernation, in heat stress tolerance, and in setting the CBT set point. In humans, the circadian rhythm of melatonin is strictly associated with that of CBT, the nocturnal decline of CBT being inversely related to the rise of melatonin. Whereas there is inconsistent evidence for the suggestion that the decline of CBT may prompt the release of melatonin, conversely, stringent data indicate that melatonin decreases CBT. Administration of melatonin during the day, when it is not normally secreted, decreases CBT by about 0.3 to 0.4°C, and suppression of melatonin at night enhances CBT by about the same magnitude. Accordingly, the nocturnal rise of melatonin contributes to the circadian amplitude of CBT. The mechanisms through which melatonin decreases CBT are unclear. It is known that melatonin enhances heat loss, but a reduction of heat production cannot be excluded. Besides actions on peripheral vessels aimed to favor heat loss, it is likely that the effect of melatonin to reduce CBT is exerted mainly in the hypothalamus, where thermoregulatory centers are located.Recentobservationshaveshownthattheacutethermoregulatoryeffects induced by melatonin and bright light are independent of their circadian phase-shifting effects. The effect of melatonin ultimately brings a saving of energy and is reduced in at least two physiological situations: aging and the luteal menstrual phase. In both conditions, melatonin does not exert its CBT-lowering effects. Whereas in older women this effect may represent an age-related alteration, in the luteal phase this modification may represent a mechanism of keeping CBT higher at night to promote a better embryo implantation and survival.

Anti-Mullerian Hormone in Premenopausal Women and After Spontaneous or Surgically Induced Menopause

Objective: The objectives of this study were: (1) to determine anti-Mullerian hormone (AMH) levels in menopausal women, and (2) to confirm the source of AMH in cycling women and its disapperance after the removal of the source. Methods: An observational and prospective study was conducted. Results: A total of 47 women were recruited for the study. The study population consisted of the following groups of patients: (A) women of late reproductive age (n= 24; mean age ± SD, 44 ± 2.8 years); (B) menopausal women (n= 14; mean age, 56 ± 4 years); (C) regularly cycling women undergoing surgical menopause (n= 9; mean age, 43 ± 4 years). Blood samples were obtained from all patients. In patients undergoing surgery, blood samples were obtained before and after surgery. AMH was undetectable in 13 of 14 postmenopausal women, whereas it was undetectacle in only two of 24 women of late reproductive age. A significant negative correlation has been found between AMH and age or follicle-stimulating hormone (FSH) in women of late reproductive age. In women who were candidates for oophorectomy, samples were obtained 3-5 days after surgery. AMH was undetectable after the surgery in all women. Conclusions: We found that AMH levels decreased in women in the late reproductive period and that menopause and ovariectomy in regularly cycling women are associated to undetectable AMH in serum. These observations confirm that the ovary could be the only source of AMH in women and that it is a novel marker for ovarian aging.

Anti-Müllerian hormone-based prediction model for a live birth in assisted reproduction

Prediction of assisted reproduction treatment outcome has been the focus of clinical research for many years, with a variety of prognostic models describing the probability of an ongoing pregnancy or a live birth. This study assessed whether serum anti-Müllerian hormone (AMH) concentrations may be incorporated into a model to enhance the prediction of a live birth in women undergoing their first IVF cycle, by analysing a database containing clinical and laboratory information on IVF cycles carried out between 2005 and 2008 at the Mother-Infant Department of University Hospital, Modena. Logistic regression was used to examine the association of live birth with baseline patient characteristics. Only AMH and age were demonstrated in regression analysis to predict live birth, so a model solely based on these two criteria was generated. The model permitted the identification of live birth with a sensitivity of 79.2% and a specificity of only 44.2%. In the prediction of a live birth following IVF, a distinction, however moderate, can be made between couples with a good and a poor prognosis. The success of IVF was found to mainly depend on maternal age and serum AMH concentrations, one of the most relevant and valuable markers of ovarian reserve.

Immunological changes and stress are associated with different implantation rates in patients undergoing in vitro fertilization–embryo transfer

OBJECTIVE To evaluate the possible correlation between immunological changes and implantation rates in patients who undergo in vitro fertilization-embryo transfer (IVF-ET). DESIGN Controlled clinical study. SETTING University hospital. PATIENT(S) Forty infertile women undergoing IVF-ET. INTERVENTION(S) Stroop Color Word (CW) test, State-Trait Anxiety Inventory (STAI) test, blood sampling. MAIN OUTCOME MEASURE(S) Heart rate and systolic and diastolic blood pressure responses to Stroop CW; circulating T, B, T-helper (CD4), and T-suppressor (CD8) lymphocytes. RESULT(S) The total number of T lymphocytes increased significantly during superovulation, resulting in significantly higher levels in subjects achieving embryo implantation than in those showing a failure of implantation. An opposite trend was observed for the activated T cells. The number of T-helper lymphocytes and the T-helper/T-suppressor ratio showed a significant increase from baseline to the time of pick-up only in patients with implantation. CONCLUSION(S) A prolonged condition of stress, which causes a decreased ability to adapt and a transitory anxious state, is associated with high amounts of activated T cells in the peripheral blood. Such a condition, in turn, is associated with a reduced implantation rate in women undergoing IVF-ET.

Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women.

The effect of melatonin on human carbohydrate metabolism is not yet clear. We investigated whether melatonin influences glucose tolerance and insulin sensitivity in aged women.