Francesco Tomei

Ultrastructural evaluation of human metaphase II oocytes after vitrification: closed versus open devices.

OBJECTIVE To compare the ultrastructural appearance of oocytes after vitrification and warming with two different devices. DESIGN Oocytes were examined by ultrastructural analysis after vitrification and warming with use of closed (CryoTip; Irvine Scientific, Santa Ana, CA) or open (Cryotop; Kitazato BioPharma Co., Ltd., Shizuoka, Japan) devices. SETTING Pordenone Hospital IVF Unit and Medical Morphological Research Department, University of Udine. PATIENT(S) Surplus oocytes from 10 patients (aged 31-39 years) undergoing assisted reproductive technologies at the Pathophysiology Unit of Human Reproduction and Sperm Bank between 2006 and 2008. INTERVENTION(S) Oocytes with normal invertoscopic appearance underwent vitrification and warming with closed (CryoTip) or open (Cryotop) devices and were processed for transmission electron microscopy. MAIN OUTCOME MEASURE(S) Cryodamage extent and cell alterations in oocytes after open or closed vitrification and warming procedures and their rehydration rate. RESULT(S) A higher rate of complete oocyte rehydration and less-severe ultrastructural alterations were observed after vitrification and warming with the open Cryotop device. CONCLUSION(S) These preliminary data suggest that oocyte ultrastructure is better preserved with an open rather than closed vitrification and warming protocol.

Renin-angiotensin system activation during severe OHSS: cause or effect?

We are really concerned about the possibility of the implementation of such preventive approach for several reasons. First, the renin-angiotensin system activation and the correlation between renin activity and OHSS severity could be, probably, the effect and not the cause of this complication. In fact, every clinical condition characterized by hypovolemia leads to a secondary reactive hyperaldosteronism by renin-angiotensin cascade activation. Severe OHSS is a model of hypovolemia produced by third space fluid shift and subsequent hematocrit increase. It is not surprising but, on the contrary, completely normal that renin activity increases in such patients.

Can we prevent premature luteinization in IVF cycles

From 1991 there is a long-lasting discussion on a possible detrimental effect of premature increase of progesterone levels during ovarian stimulation in IVF. A recent meta-analysis of more than 60,000 cycles states that premature progesterone increase reduces pregnancy rates starting from P4 values of 0.8 ng/ml. The detrimental effect seems to be related to endometrial receptivity impairment according to lack of detrimental effect on oocytes competence in ovodonation. Embryo freezing and deferred embryo transfer on artificial endometrium permits to avoid this detrimental effect but the cycle has to be segmented in two phases. Moreover embryo freezing is an extra burden for IVF lab and could induce embryo damage. So the implementation of an effective pharmacological treatment to prevent premature luteinization could be very interesting for our daily ART practice. On the basis of so far available literature data and our preliminary proof of concept experience we suggest that metformin (1000-1500 mg daily) from first monitoring until ovulation triggering could be suitable for this purpose irrespective of ovarian reserve of the patient.

Homologous in vitro fertilization in Turner syndrome: insights from a case report

OBJECTIVE To describe a bigeminal pregnancy obtained with a homologous intracytoplasmic sperm injection cycle in a patient with high-grade mosaic Turner syndrome (45,XO/47,XXX 97.5%/2.5%) with bicuspid aortic valve. DESIGN Case report. SETTING Unit of Pathophysiology of Human Reproduction in a general hospital. PATIENT(S) Patient with mosaic Turner syndrome with bicuspid aortic valve. INTERVENTION(S) Homologous intracytoplasmic sperm injection cycle after controlled ovarian hyperstimulation with a GnRH agonist flare-up depot protocol and menotropins. MAIN OUTCOME MEASURE(S) Pregnancy development, echocardiographic monitoring of aortic root, karyotypes of progeny. RESULT(S) Ongoing bigeminal pregnancy with the delivery of two healthy infants (46,XX and 46,XY, respectively) by cesarean section without any cardiovascular complication or aortic root echocardiographic modification in the mother. CONCLUSION(S) Even in patients with Turner syndrome with high-grade 45,XO mosaicism and reduced ovarian reserve, a trial of homologous reproduction should be offered after a thorough cardiologic evaluation to avoid pregnancy-related cardiovascular complications.

Comparison of protocols efficacy in poor responders: differences in oocytes/embryos competence with different protocols, a retrospective study.

At present, there is no agreement on poor ovarian response definition, and no definitive evidence that this prognosis can be changed by a specific protocol. Our data suggest that a flare-up protocol with a depot gonadotropin-releasing hormone (GnRH) agonist formulation gives higher total pregnancy and implantation rates than a GnRH antagonist, possibly by improving oocyte/embryo competence.

Ovarian Hyperstimulation Syndrome: The Best Approaches for Preven-tion and Treatment: A Mini-Review

Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic disorder resulting from ovarian stimulation during assisted reproductive techniques (ARTs). It can result in renal failure, thromboembolic phenomena, adult respiratory distress syndrome and, occasionally, death. Almost all previous preventive strategies resulted ineffective. Vascular Endothelial Growth Factor (VEGF) plays a pivotal role in the pathophysiology of this syndrome so VEGF antagonism has been suggested for OHSS prevention. Since VEGF is also a physiological regulator of folliculogenesis, progesterone secretion and endometrial angiogenesis, its complete inactivation by monoclonal antibodies could produce potential undesirable effects. Administration of Human Chorionic Gonadotropin (HCG) stimulation of VEGF production is fatal for the developing of OHSS; the use of GnRH agonist instead of HCG for ovulation triggering, is a promising strategy. Recently dopamine D2 agonists have been shown to counteract VEGF induced vascular permeability. The lack of toxic or teratogenic effects could make cabergoline an effective and safe aetiological approach for OHSS prevention/treatment. A recent meta-analysis has indicated that the administration of metformin significantly prevents OHSS development in polycystic ovary syndrome, an high risk group. In the light of these new studies we believe that recent guidelines on OHSS prevention need a substantial revision.