Charlotte Sonigo

Hyperprolactinemia-induced ovarian acyclicity is reversed by kisspeptin administration

Hyperprolactinemia is the most common cause of hypogonadotropic anovulation and is one of the leading causes of infertility in women aged 25-34. Hyperprolactinemia has been proposed to block ovulation through inhibition of GnRH release. Kisspeptin neurons, which express prolactin receptors, were recently identified as major regulators of GnRH neurons. To mimic the human pathology of anovulation, we continuously infused female mice with prolactin. Our studies demonstrated that hyperprolactinemia in mice induced anovulation, reduced GnRH and gonadotropin secretion, and diminished kisspeptin expression. Kisspeptin administration restored gonadotropin secretion and ovarian cyclicity, suggesting that kisspeptin neurons play a major role in hyperprolactinemic anovulation. Our studies indicate that administration of kisspeptin may serve as an alternative therapeutic approach to restore the fertility of hyperprolactinemic women who are resistant or intolerant to dopamine agonists.

Prolactin signaling mechanisms in ovary.

Prolactin is a hormone that is essential for normal reproduction and signals through two types of receptors. Not only is the classical long form of the prolactin receptor identified, but so are many short form receptors in rodents and human tissues. Mouse mutagenesis studies have offered insight into the biology of prolactin family, providing compelling evidence that the different isoforms have independent biological activity. The possibility that short forms mediate cell proliferation is important for a variety of tissues including mammary gland and ovarian follicles. This review summarizes our current knowledge about prolactin signaling and its role in reproduction through either long or short isoform receptors.

Fertility preservation in Turner syndrome

Premature ovarian insufficiency is a relatively rare condition that can appear early in life. In a non-negligible number of cases the ovarian dysfunction results from genetic diseases. Turner syndrome (TS), the most common sex chromosome abnormality in females, is associated with an inevitable premature exhaustion of the follicular stockpile. The possible or probable infertility is a major concern for TS patients and their parents, and physicians are often asked about possible options to preserve fertility. Unfortunately, there are no recommendations on fertility preservation in this group. The severely reduced follicle pool even during prepubertal life represents the major limit for fertility preservation and is the root of numerous questions regarding the competence of gametes or ovarian tissue crybanked. In addition, patients suffering from TS show higher than usual rates of spontaneous abortion, fetal anomaly, and maternal morbidity and mortality, which should be considered at the time of fertility preservation and before reutilization of the cryopreserved gametes. Apart from fulfillment of the desire of becoming genetic parents, TS patients may be potential candidates for egg donation, gestational surrogacy, and adoption. The present review discusses the different options for preserving female fertility in TS and the ethical questions raised by these approaches.

History of ABVD alters the number of oocytes vitrified after in vitro maturation in fertility preservation candidates

AIM This retrospective case-control study aimed at analyzing the results of in vitro maturation (IVM) of oocytes, used for fertility preservation (FP), in patients with history of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) for classical Hodgkin lymphoma. PATIENTS & METHODS A total of 22 candidates for FP, having received ABVD at least 2 years before IVM for FP were studied. IVM results were compared with those of 44 breast cancer patients, without history of chemotherapy, matched for ovarian reserve parameters. RESULTS The number of cumulo-oocyte complexes recovered and the total number of matured oocytes vitrified was lower in patients having received AVBD (5.5 ± 4.8 vs 8.5 ± 4.4 oocytes; p = 0.03 and 3.5 ± 3.7 vs 6 ± 3.0 oocytes; p < 0.04, respectively). CONCLUSION In light of these results, FP should be discussed before ABVD.

The past, present and future of fertility preservation in cancer patients

Fertility preservation strategies have been developed for men and women whose fertility is compromised for medical reasons, especially in case of cancer therapy. At present, many reliable options for preserving fertility are available. However, a part of these fertility preservation methods, despite being promising, are still considered experimental. Nevertheless, there are still situations where no methods can be offered. Remarkable scientific progress is currently underway to improve available techniques and to develop new technologies to solve problems with current fertility strategies. These new options may drastically change reproductive options for young patients facing germ cell loss and hence sterility. Therefore, oncofertility counseling by a specialist is recommended for all young cancer patients having to undergo treatment that may reduce fertility potential.

Should metaphase 1 and 2 stages oocytes be vitrified in the same time for fertility preservation

AIMS Could metaphase 1 (M1) and 2 (M2) stages oocytes from in vitro maturation (IVM) cycles and controlled-ovarian hyperstimulation (COH) cycles be frozen at the same time without any adverse effect of vitrification on further survival (SR) and maturation rates (MR)? MATERIALS & METHODS M1 from cancer patients were prospectively included in IVM/COH groups, and in study or control subgroups if they were vitrified or not. In each study subgroup, SR were compared with that of M2 oocytes vitrified/warmed from egg donors. MR were compared with those of fresh-M1 oocytes from control IVM/COH subgroups. RESULTS SR were not different between groups. MR compared respectively between survived- and fresh-M1 oocytes were similar when resulting from COH (85.2 vs 81.1%) but significantly lower after IVM (39.1 vs 73.3%). CONCLUSION Simultaneous freezing of M1/M2 oocytes could be applied to COH but not to IVM during the course of fertility preservation.

Delivery rates after elective single cryopreserved embryo transfer related to embryo survival

OBJECTIVE The objective of this study was to assess if eSCET (elective Single Cryopreserved Embryo Transfer) outcome is related to blastomere survival rate. The final objective was to avoid multiple pregnancies and offer the best chances to women to achieve pregnancy even during their frozen-thawed embryo transfer (FET) cycles. STUDY DESIGN Patients were included in this prospective observational study if they met the following criteria: (i) women age <37 years old; (ii) IVF of ICSI cycle rank ≤2, (iii) eSET proposed during fresh embryo transfer cycle and (iv) ≥1 good quality cryopreserved embryos available (<20% fragmentation and 4-5 blastomeres at day-2 or 7-9 blastomeres at day-3). Live birth rates (LBR) were compared into eSCET groups according to embryo survival (partially damaged or intact transferred embryo). RESULTS We observed among selected patients, that partial loss of blastomeres (1 blastomere for day-2 embryos, 1 or 2 blastomeres for day-3 embryos) following FET cycles did not affect LBR compared with intact embryo. CONCLUSION These results underline the relevance of eSCET as a strategy to reduce multiple pregnancies frequency without reducing LBR.

Freezing oocytes or embryos after controlled ovarian hyperstimulation in cancer patients: the state of the art

Quality of life of young cancer survivors has become a major issue. However, anticancer therapies can have a detrimental impact on fertility. It is now well-established that all patients should receive information about the fertility risks associated with their cancer treatment and the fertility preservation options available. Currently, oocyte or embryo banking after controlled ovarian hyperstimulation represents the most effective method for preserving female fertility. Over the past years innovative protocols of ovarian stimulation have been developed to enable cancer patients to undergo oocyte or embryo cryopreservation irrespective of the phase of the cycle or without exogenous follicle-stimulating hormone-related increase in serum estradiol levels. The present article reviews the different protocols of ovarian hyperstimulation for cancer patients, candidates for fertility preservation.

Hypothalamic-Pituitary-Ovarian Axis Reactivation by Kisspeptin-10 in Hyperprolactinemic Women With Chronic Amenorrhea

Context: Hyperprolactinemia-induced hypogonadotropic amenorrhea (hPRL-HA) is a major cause of hypothalamic gonadotrophin-releasing hormone (GnRH) deficiency in women. In hyperprolactinemic mice, we previously demonstrated that hypothalamic kisspeptin (Kp) expression was diminished and that Kp administration restored hypothalamic GnRH release, gonadotropin secretion, and ovarian cyclicity, suggesting that Kp neurons could also play a role in hPRL-HA. Objective: To study the effect of Kp-10 on the gonadotropic-ovarian axis in women with hPRL-HA. Patients: Two women (32 and 36 years old) with chronic hPRL-HA (prolactin: between 94 and 102 and 98 and 112 ng/mL, respectively) caused by cabergoline-resistant microprolactinomas. Interventions: Cabergoline was discontinued 6 months before inclusion. Blood samples were taken every 10 minutes for 12 hours during 2 consecutive days to evaluate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Serum estradiol (E2), testosterone (T), and inhibin B (IB) levels were also measured. Vehicle or Kp-10 (1.5 μg/kg/h) was infused intravenously for 12 hours. Results: Kp-10 induced a significant increase in LH and FSH levels and increased LH pulses. E2, T, and IB serum levels were also significantly increased. Conclusions: In this exploratory study, we demonstrated that administration of Kp-10 reactivated gonadotropin secretion in women with hPRL-HA and increased ovarian activity. Our data suggest that, as in rodents, GnRH deficiency in hPRL-HA is also mediated by an impairment of hypothalamic Kp secretion. Kp-10 or its analogues could have therapeutic application as an alternative approach to restore ovarian function and fertility in women with hPRL-HA resistant to dopamine agonists and in whom pituitary surgery is not possible.

Fertility Preservation in Women

Fertility preservation is a fast growing discipline with the purpose of offering different techniques for women facing with pathologies or treatments threatening their fertility. Recent advances in fertility preservation techniques have led to a widespread of indications. Fertility preservation should now be considered not only for women having to receive gonadotoxic treatments for cancer but also in genetic or endocrine disorders, as well as benign ovarian diseases at risk of premature ovarian insufficiency. These situations could lead medical and ethical concerns and need for multidisciplinary management.