The role of mitochondrial activity in female fertility and assisted reproductive technologies: overview and current insights.

Mitochondria have been implicated as key factors regulating female reproductive processes. Notable progress has been made in determining the role of mitochondria with respect to oocyte maturation, fertilization and early embryo development. In addition, mitochondrial function and dysfunction has been the subject of various studies in ovarian ageing and metabolic stress models. However, the overall mitochondrial impact on female fertility is yet to be uncovered. The mitochondrial DNA content of granulosa, cumulus and trophectoderm cells is being explored as a biomarker of oocyte quality and embryo viability. As growing evidence suggests that embryo potential could be related to the ability of oocyte mitochondria to generate energy, efforts have been made to investigate the possibility of improving mitochondrial capacity in women with poor outcomes after treatment with assistedreproductive technologies. Thus far, therapeutic attempts have focused mainly on using nutrients to restore mitochondrial function and transferring mitochondria from autologous germline precursor cells. Moreover, new perspectives on optimizing infertility treatments have arisen with modern mitochondrial replacement therapies, which are being applied in women with mitochondrial disease-causing mutations. This review explores aspects of the distinctive contribution of mitochondria to reproductive processes and discusses current and emerging clinical implications.

Review: follicular waves in the human ovary: a new physiological paradigm for novel ovarian stimulation protocols.

Ovulation induction (OI) is a cornerstone of human assisted reproduction treatments (ART). Current OI protocols are based on the human follicular dynamics model known as propitious moment theory (PMT), by which follicles continuously grow from the primordial pool without any pattern, and follicular fate depend on the occurrence of a gonadotropin surge. Recently, a new paradigm of human follicular dynamics called follicular waves was revealed using sequential ultrasound examination of 1 interovulatory interval. Instead of random growth, follicles develop in coordinated groups or waves, occurring 2 to 3 times during an interovulatory interval. Follicular waves are common in several other mono-ovulatory species, like equines and bovines. In fact, this model was applied to the development of several OI protocols in veterinary medicine, especially in cows. It has been shown that synchronization of OI with the emergence of a follicular wave increases substantially success rates in animals, even with single embryo transfer. Veterinarians have already developed mechanisms to control wave emergence through mechanical or chemical ablation of the dominant follicle or corpus luteum. Considering the follicular dynamics similarities between humans and bovines regarding the follicular wave phenomenon, we hypothesize that synchronization of follicular wave emergence with ovarian stimulation produces more competent oocytes and embryos and will enhance ART efficiency in humans. At the end of this article, we propose 2 theoretical approaches to induce the emergence of a follicular wave in women: (1) a mechanical strategy by aspiration of the dominant follicle and (2) a pharmacological strategy by administering estradiol and progesterone.

Nonobese women with polycystic ovary syndrome respond better than obese women to treatment with metformin.

OBJECTIVE: To determine the clinical, hormonal, and biochemical effects of metformin therapy in obese and nonobese patients with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Department of Gynecology of Federal University of São Paulo, São Paulo, Brazil. PATIENT(S): Twenty-nine patients with PCOS. INTERVENTION(S): Patients were treated with 500 mg of p.o. metformin t.i.d. for 6 months. MAIN OUTCOME MEASURE(S): Clinical data as well as serum concentrations of sex steroids, sex hormone-binding globulin (SHBG), gonadotropins, leptin, GH, lipids, insulin, and glucose levels were assessed before and after treatment. RESULT(S): In the metformin group of nonobese patients, the mean fasting serum insulin concentration decreased from a pretreatment value of 12.1 +/- 2.4 to 6.3 +/- 0.6 microU/mL after treatment, and the area under the curve of insulin decreased from 5,189.1 +/- 517.4 to 3,035.6 +/- 208.9 microU/mL per minute. Also in the metformin group of nonobese patients, the mean basal serum total testosterone, free testosterone, and androstenedione concentrations decreased by 38%, 58%, and 30%, respectively. In the obese patients treated with metformin, only free testosterone showed a statistically significant decrease (1.7 +/- 0.2). CONCLUSION(S): Our data suggest that nonobese patients respond better than obese patients to a 1.5 g/day metformin regimen.