March 24th/25th, 2010 - Tel Aviv, Israel
Update in Infertility – ART
The MSRM Tel Aviv workshop was the first activity of the MSRM in Israel. The idea of having an MSRM workshop in Israel was discussed in the meeting of the members of the executive committee of the MSRM society during the annual congress in Hammamet, Tunisia - May, 2008. The workshop in Tel Aviv took place in the “Beth Shalom” Auditorium on the 24th and 25th of March, 2010. There were 132 participant from 12 countries around the Mediterranean sea and Europe. The topics discussed were about folliculogenesis, oocyte, sperm, embryo and implantation, endoscopy in infertility and endometriosis from both points of view, the endoscopic approach of treatment and embryo quality – implantation.
Prof. Y.Orli (Israel) described the progression in the knowledge of the follicular development from the days of Graff till nowadays with the different checkpoints and gene signaling. The endocrine aspects of folliculogenesis were reviwed by Prof. I.Messinis (Greece). Apoptosis in folliculogenesis and production of steroids seem to play an active role in ovarian psycological functions. P53, WTl, Bel-2 and adhesions molecules are implicated through regulation of apoptosis in folliculogenesis as shown by Prof. A.Makrigiannakis (Greece). In the session of sperm Prof. M.Huleihel (Israel) showed how Soft Agar Culture System can be considered as a novel in vitro system for growth, proliferation and differentiation of premeiotic mouse male germ cells into meiotic and post-meiotic stages including spermatozoa with intact acrosome.
Dr. E.Goossens (Belgium) showed that OMSO is the cryoprotectant of choice for freezing testicular tissue to get the highest survival of spermatogonial stem cells. With specific methods,the isolation of germ cells only without the malignant cells is feasible. The technique of injecting cell suspentions through the rete testis has stilI to be improved or modified since results are not satisfactory. However, grafting of testicular tissue can be done if the risk for malignant cells in the biopsy is excluded. There is evidence of reproduction after the transplant of spermatogonia sperm cells. However the success is decreased compared with fertile males because of a lower sperm count and motility. The role of Intracytoplasmic Morphologically Selelcted Sperm Injection (IMSI) is stilI questionable and caused many discussions in the recent years. While so far, there are no randomized controlled studies, Dr. R.Maggiulli (Italy) brought their experience with an RCT performed in their centre, where the contribution of IMSI was clearly not demonstrated in terms of implantation, pregnancy or abortion rate.
Results from different centres have shown contradictory effects of vacuoles on sperm competence. Moreover sperm nuclear defects visible by IMSI did not correlate with chromosomal abnormalities,or presence of DNA breakage. The session of the oosyte started with the review of chilling injuries and vitrification of the oocyte, given by Prof. A.Arav (Israel). It continued with the description of polrization microscopy by Prof. M.Montag (Germany) demonstrating that it is a good tool for the evaluation of important laboratory parameters. Spindle and zona pellucida are prognostic criteria for oocyte maturation and embryo potentiaI to implant. Dr. Y.Shufaro (Israel) reviewed the information available about oocyte formation from embryonic stem cells. Few have succeded in mouse model. However, the product is stilI problematic. In any mode, the potential of this is great for research and reproduction. Dr. L.Nardo (UK) discussed the relation between AMH as a predictor of ovarian performance and embryo quality. Dr. R.Maggiulli (Italy) showed the results of pregnancy outcome from yitrified oocyte which were comparable with those from fresh oocytes.
In the session of implantation Prof. M.Montag (Germany) showed us the preliminary results of polar body biopsy and CGH.
Results of this multi centric study will be shown in ESHRE meeting in Rome. Dr. R.Maggiulli (Italy) demonstrated that oocyte morphology assessed on the day of fertilization is not an indicator of oocyte competence. Embryo morphology is much more powerful for assessment of implantation likelihood. Dr. J.A. Horcajadas (Spain) spoke about the implantation faliure. He showed the high number of genes that are involved with endometrial receptivity, the genes which are expressed in stimulated cycles, and those which are involved in cases with repeated implantation faliure. This profile of genes can be studied by microarray technique which enables to check endometrial receptivity in concrete cases. Dr. Y.Gnainski (Israel) showe the possible mode how endometrial biopsy may have an impact on implantation. The biopsy of the endometrium increases the secretion of TNF which leads to an infiammatory reaction including the concentrations of monocytes, macrophages and dendritic-like cells which lead to the expression of genes involved in implantation. Their presence is crucial for a successful implantion. Prof. A.Makrigiannakis (Greece) described different modaIities to improve implantation and showed first results with a new agent for this purpose as Corticotropin-releasing hormone. During the second day of the Tel Aviv MSRM workshop a parallel session was dedicated to the minimally invasive procedures and dilemmas regarding mechanical infertility.
The session was moderated by Dr. Moty Pansky (Israel , head of the Gyn Endoscopy in Assaf Harofe MedicaI Centre with an active participation of the international and local faculty. The openaning lecture was given by Dr. A.Watrelot (France), the chairman of MSRM, who summarized his vast experience using the Fertiloscopy technique. Dr. R.Mashiach (Israel) gave an update about intraumal fibroids and the relation to infertility and discussed the need for conservative myomectomy. Dr. C.Goldchmit (Israel) raised important issues regarding the need to perform salpingectomy in IVF patients or either tuboplasty in selected cases.
The second session was dedicated o the unsolved problem of pelvic and intrauterine adhesion, Dr. V.Tanos (Cyprus) reviewed the causes, complications and some novel treatment of Asherman Syndrome. Dr. A.Setùbal (Portugal) addressed the unsolved problem of peritoneaI adhesions, its formation mechanism and showed the new modalities and medicaI agents to decrease adhesion formation. In the last part of “Endoscopy in Infertility" an expert panel was moderated by Prof. A.Golan and Dr. M.Pansky (Israel). The members of the panel were Prof. M.Goldenberg (Israel) and Prof. N.Rojansky (Israel), Dr. A.Watrelot (France) and Dr. A.SetùbaI (Portugal). Four clinical cases were discussed: Intrauterine septum whether to remove it prior to IVF, recurrent severe intrauterine adhesions, mid-size recurrent endometriomal cyst and removal of fibroids prior to IVF treatment. The pros and cons were discussed.The lively discussions showed that solutions are not "unisonic". However, alI participants agreed that the sessions were fruitful, interesting and a platform for future considerations. The finaI session of was about endometriosis.
Prof. B.Rizk (originally from Egypt, now from USA) spoke about the use of transvaginal sonography to diagnose endometriomas. MRI is useful diagnosing rectovaginaI endometrosis. Most of the protein molecules in the peritoneal fluid are with immune response. Several protein isoforms have different expression in the mild than in the severe form of the endometriosis.
Proteomics will have an important role in the diagnosis of endometriosis. Prof. B.Rizk (USA), in his second presentation, showed how endometriosis has a negative impact on the outcome of ART in terms of decreasing the number and quality of the oocyte and poor endometrial quality. Removal'of small endometriomas (<3 cm) prior to IVF treatment has no benefit. Aggressive surgery may decrease pronouncedly ovarian reserve. Dr. L. Nardo (UK) showed the changes of the endometrium occurring in women with endometriomas. The endometrium is deregulated as shown by aberrant glycsylation: Prolonged GnRH agonists may regulate the endometriaI environment for successful lastocyst implantation. Dr. A.Watrelot (France) spoke about endometriosis without symptoms which can effeçt fertility. Dr. A.Setùbal (Portugal) concluded the session by showing that in mild to moderate endometriosis surgery or no treatment are better than medicaI treatment. In severe endometriosis, surgery is important for pain relief, but has no impact on fertility.