Age-dependent alterations in the signaling patway involved in oocyte activation.

Female reproductive aging is characyterized by the reduction of quality and quantity of ovarian follicle pool. This condition jeopardizes the production of oocytes competent for fertilization and embryi development. Following ovulation, mammallian oocytes are arrested at metaphase of the second meiotic division. Interaction with sperm or exposure to parthenogenetic agents triggers the activation of a calcium dependent pathway leading to meiosis resumption and entry into the first embryonic cell cycle. In this study we evaluated the hypotesis that the reduced devlopmental competence of "old" oocytes might be related to the reduced ability to stimulate signalling patways underlying oocyte activation. Since a key component of this pathway is the protein kinase C (PKC), we hypothesized that "old" oocytes fail in activating correctly this enzyme. To this end, we compared the effect of SrCL2, a parthenogenetic agent, on ovulated oocytes collected from "young" and old mice. Analysis of the kinetic of meiotic progression , revealed a significant delay in meiosis resumption and a reduced percentage of pronuclei formation in oocytes from old mice. This change was associated with a reduced expression of the calcium-dependent PKC isoforms monitored by means of Western blotting analysis. Moreover, old oocytes were characterized by an altered pattern of PCK activation. BAsed on present results, we suggest that oocytes produced during advanced reproductive aging may suffer from an incorrect storage of PKC during oogenesis that can impair the process of oocytes activation. Since age -dependent changes in PKC activation were found also in endpthelial and neuronal cells our data support the idea that mechanism underlying aging of germ cells resembles those present in somatic cells. In conclusion, present study might contribute to the knowledge of molecular markers of oocyte aging that could be helpful for setting new approches in IVF treatments of old patients

Ovulation induction with pulsatile gonadotrophin-releasing hormone (GnRH) in women with hypothalamic amenorrhea

Aim of the study: We studied ovulation and pregnancy rates following follicular maturation by administration of pulsatile gonadotrophin-releasing hormone (GnRH) in women with hypothalamic amenorrhea (HA). Material and methods: A total of 31 patients presenting documented HA were treated between January 1989 and December 1995. One to six cycles for a total of 103 cycles were stimulated by GnRH administrated at a dose of 20 µg/pulse every 90 minutes in follicular phase, and every 120 minutes 3-5 days after the ovulation. Luteal phase was supported by 1000 IU HCG/48h (Profasi, Serono). Each cycle was monitored using estradiol (E2), progesterone (P), luteinizing hormone (LH) assays and vaginal echography. Ovulation was confirmed when E2 level > 0,8 nmol/l was observed in the presence of an LH peak and when a follicle > 18 mm in diameter was observed by vaginal echography. When no male factor was observed (n=18) sexual intercourse was recommended. In case (n=13) of associated male infertility (number of normal or motile spermatozoa recovered < 5.106) one insemination was performed 24 to 36 hours after the ovulation criteria have been observed. Results: Ovulation and pregnancy rates were respectively 81% (n=84) and 21% (n=22). Six (6%) biochemical pregnancies were observed. Spontaneous abortion occurred in 7 (7%) cases. Fourteen full term deliveries were obtained (15%) and one pregnancy is ongoing. Conclusion: In our opinion, pulsatile GnRH is an efficient and safe treatment of anovulation in HA patients. Neither multiple pregnancy nor ovarian hyperstimulation syndrome (OHSS) have been observed. Pulsatile GnRH administration allows to obtain high rates of ovulation and conception

Recurrent ovarian torsion in a pregnancy complicated by ovarian hyperstimulation syndrome

We report a case of recurrent left adnexal torsion in a pregnancy complicated by ovarian hyperstimulation syndrome (OHSS). The patient underwent laparoscopic surgery twice, the first time her enlarged left adnex was relocated, then salpingo-oophoropexy was performed. Adnexa were conserved successfully and the patient delivered a healthy baby

Does supplementation with recombinant luteinizing hormone prevent ovarian hyperstimulation syndrome in down regulated patients undergoing recombinant follicle stimulating hormone multiple follicular stimulation for IVF/ET and reduces cancellation rate for high risk of hyperstimulation?

Aim of this study was to assess the efficacy of recombinant luteinizing hormone (rLH) supplementation in late follicular phase in multiple follicular stimulation with recombinant follicle stimulating hormone (rFSH) in Triptoreline down-regulated patients undergoing IVF, on preventing clinical OHSS and cycles cancellation for OHSS risk. Nine hundred ninety-nine patients aged ≤ 40 with basal FSH ≤ 12 mUI/Ml were down-regulated before starting rFSH stimulation for oocytes recovery. Patients were allocated in two groups: (A) (501 patients) treated with 150 IU of rFSH eventually adjusting rFSH dosage day 7 of stimulation until recombinant human chorionic gonadotropin (rhCG) administration, (B) (498 patients) treated with 150 IU of rFSH and 75 IU of rLH since day 7 of stimulation until rhCG administration and adjusting rFSH at the same day. E2 the day of rhCG was higher in group B (p < 0.0001); number of cycles cancelled in group A (42/8.3%) for risk of ovarian hyperstimulation syndrome (OHSS) was higher than group B (12/2.4%) (p < 0.000001). We observed an increase in pregnancies in group B compared with group A (16.8% vs 11.9%) (p < 0.05) and we observed also a larger number of clinical OHSS in group A than in group B (p < 0.05). PMID: 21391759 [PubMed - in process

Non invasive diagnosis by Doppler ultrasonography of fetal anemia due to massive fetomaternal hemorrhage in a case of twin-to-twin transfusion syndrome treated with serial amnioreduction

Massive fetomaternal hemorrhage is a rare condition occurring during pregnancy and severe fetal anemia, hydrops and death may occur. Case: We report a case of massive fetomaternal hemorrhage due to serial amnioreduction in a pregnancy complicated by stage IV twin-to-twin transfusion syndrome. Fetomaternal hemorrhage occurred at 23 + 4 weeks of gestation as a consequence of the second amnioreduction, which determined a chronic blood loss in the placental puncture site. Moreover the middle cerebral artery peak systolic velocity vales of both twins began to increase after the amnioreduction indicating severe anemia in the recipient twin and mild anemia in the donor twin after the fourth amnireduction. The Kleihauer-Betke stain showed 5% fetal cells in maternal circulation, indicating a fetomaternal hemorrhage of 120 ml. Emergent cesarean section has been performed at 25 + 5 weeks of gestation because of placental abruptio and hemoglobin levels confirmed severe and mild anemia in the recipient and donor twin, respectively. We conclude that Doppler assessment of the middle cerebral artery peak systolic velocity should diagnose fetal anemia due to fetomaternal hemorrhage in a non-invasive fashion and time the need of invasive procedur

The Prevention of Gestational Diabetes

Abstract The negative impact of the gestational diabetes on the maternal and fetal health is well known and this impact is closely related to gestational age at which the diagnosis is done. Therefore, the use of therapeutic options able to prevent or delay the gestational diabetes occurrence has a positive impact on maternal and neonatal outcomes. a non-pharmacological option and have a positive impact on insulin resistance although they do not seem to prevent the gestational diabetes onset.The preconceptional use of metformin in women with polycystic ovary syndrome protects the pancreatic beta cell reserve preventing or delaying the occurrence of gestational diabetes. However, there are also doubts on the drug safety in pregnancy since it completely crosses the placenta.From this point of view, the inositol could represent an excellent alternative.Its role as insulin sensitizing agent is well documented on improving both the hormonal and reproductive parameters. However, the studies on its preconc