Gian Luigi Marchino

Laparoscopic stripping of endometriomas negatively affects ovarian follicular reserve even if performed by experienced surgeons

In order to estimate the impact of laparoscopic stripping of endometriomas on the ovarian follicular reserve, 43 normo-ovulatory women were studied by endocrine (anti-Müllerian hormone (AMH), FSH, LH, inhibin B, oestradiol) and ultrasonographic (antral follicle count (AFC)) methods before surgery, and 3 and 9 months after surgery. The operation was performed by experienced laparoscopists, particularly aware of the need to avoid damaging the healthy part of the ovary. Serum AMH concentrations significantly decreased after the operation (1.4±0.2 ng/ml after 3 months and 1.3±0.3 ng/ml after 9 months versus 3.0±0.4 ng/ml before surgery; P<0.0001), whereas basal FSH, LH, oestradiol and inhibin B concentrations remained unchanged. The volume of the operated ovary significantly diminished after surgery (P<0.0001), whereas the AFC was not significantly altered. Overall, the data show that laparoscopic stripping of endometriomas reduces ovarian reserve. The significant decrease of AMH after surgery confirms that part of the healthy ovarian pericapsular tissue, containing primordial and preantral follicles, is removed or damaged despite all the surgical efforts to be atraumatic. This must be carefully considered when laparoscopic cystectomy surgery is scheduled for patients with no relevant symptoms besides infertility or with already small ovarian reserve.

Live birth after orthotopic grafting of autologous cryopreserved ovarian tissue and spontaneous conception in Italy

OBJECTIVE To describe a live birth obtained in Italy after autologous orthotopic transplantation of cryopreserved ovarian cortical tissue. DESIGN Case report. SETTING University department of gynecology and obstetrics, reproductive medicine and IVF unit. PATIENT(S) A 29-year-old patient affected by β-thalassemia (intermedia phenotype) who underwent chemotherapy and bone marrow transplantation at age 21 years, resulting in a complete precocious ovarian failure. INTERVENTION(S) Before being treated with chemotherapy (busulfan, cyclophosphamide, and cyclosporine) for bone marrow transplantation, the patient underwent laparoscopic sampling of ovarian cortical tissue that was frozen and cryopreserved in liquid nitrogen. Eight years later, the ovarian tissue was thawed and grafted during laparoscopy at an orthotopic site. MAIN OUTCOME MEASURE(S) Ultrasound and endocrine monitoring of the postgrafting restoration of ovarian function; conception, pregnancy, and live birth. RESULT(S) Three months after grafting, the decrease of circulating FSH levels and the parallel increase of E(2) levels demonstrated ovarian function restoration, which was confirmed by bidimensional ultrasound and color Doppler examinations. After some ovulatory cycles, the patient spontaneously conceived 16 months after transplantation. After 39 weeks of uneventful gestation, a healthy girl weighing 3,970 g was born. CONCLUSION(S) Autologous grafting of cryopreserved ovarian cortex at an orthotopic site may allow ovarian function restoration, spontaneous conception, and birth of a healthy baby.

Hysteroscopy in recurrent in-vitro fertilisation failure (TROPHY): a multicentre, randomised controlled trial

BACKGROUND The success rate of in-vitro fertilisation (IVF) remains low and many women undergo multiple treatment cycles. A previous meta-analysis suggested hysteroscopy could improve outcomes in women who have had recurrent implantation failure; however, studies were of poor quality and a definitive randomised trial was needed. In the TROPHY trial we aimed to assess whether hysteroscopy improves the livebirth rate following IVF treatment in women with recurrent failure of implantation. METHODS We did a multicentre, randomised controlled trial in eight hospitals in the UK, Belgium, Italy, and the Czech Republic. We recruited women younger than 38 years who had normal ultrasound of the uterine cavity and history of two to four unsuccessful IVF cycles. We used an independent web-based trial management system to randomly assign (1:1) women to receive outpatient hysteroscopy (hysteroscopy group) or no hysteroscopy (control group) in the month before starting a treatment cycle of IVF (with or without intracytoplasmic sperm injection). A computer-based algorithm minimised for key prognostic variables: age, body-mass index, basal follicle-stimulating hormone concentration, and the number of previous failed IVF cycles. The order of group assignment was masked to the researchers at the time of recruitment and randomisation. Embryologists involved in the embryo transfer were masked to group allocation, but physicians doing the procedure knew of group assignment and had hysteroscopy findings accessible. Participants were not masked to their group assignment. The primary outcome was the livebirth rate (proportion of women who had a live baby beyond 24 weeks of gestation) in the intention-to-treat population. The trial was registered with the ISRCTN Registry, ISRCTN35859078. FINDINGS Between Jan 1, 2010, and Dec 31, 2013, we randomly assigned 350 women to the hysteroscopy group and 352 women to the control group. 102 (29%) of women in the hysteroscopy group had a livebirth after IVF compared with 102 (29%) women in the control group (risk ratio 1·0, 95% CI 0·79-1·25; p=0·96). No hysteroscopy-related adverse events were reported. INTERPRETATION Outpatient hysteroscopy before IVF in women with a normal ultrasound of the uterine cavity and a history of unsuccessful IVF treatment cycles does not improve the livebirth rate. Further research into the effectiveness of surgical correction of specific uterine cavity abnormalities before IVF is warranted. FUNDING European Society of Human Reproduction and Embryology, European Society for Gynaecological Endoscopy.

Salpingoscopic and Laparoscopic Investigations in Relation to Fertility Outcome

STUDY OBJECTIVE To evaluate the correlation between salpingoscopic and laparoscopic findings and their relation to reproductive outcomes. DESIGN Prospective study (Canadian Task Force classification II-2). SETTING University-affiliated hospital. PATIENTS Ninety-one infertile women. INTERVENTION Salpingoscopy and laparoscopy. MEASUREMENTS AND MAIN RESULTS Salpingoscopic findings were expressed according to a widely used classification. Tubal morphology at laparoscopy was defined as regular (normal morphology), convoluted (any kind of distortion or adhesion), or hydrosalpinx. Laparoscopic and salpingoscopic findings did not correlate. Seventeen pregnancies occurred within 1 year from the procedures. According to life table analysis, the cumulative pregnancy rate was significantly higher in women with endotubal morphology showing minimal or no tubal damage, than in women with higher grades of endotubal damage. Conversely, tubal morphology at laparoscopy was not able to predict pregnancy outcome. CONCLUSION Laparoscopy alone might not be sufficient to predict tubal integrity. Performing salpingoscopy with laparoscopy could significantly increase accuracy in predicting short-term fertility outcome. Given its low complication rate and brief duration, salpingoscopy should have a primary role in management of infertility.

A slowly reabsorbed, echogenic surgical thread provides a long-lasting ultrasound- detectable marker of grafted ovarian tissue

This communication reports a novel technical solution for the orthotopic transplant of cryostored-thawed ovarian tissue. The described technique was applied to three young women with iatrogenic ovarian failure. An echogenic thread that is reabsorbed after 6 months was used to fasten the thawed ovarian small fragments before grafting them onto the atrophic ovary. This technical solution made it possible to avoid the loss of small tissue pieces during laparoscopic grafting as well as to precisely localize the grafted tissue by transvaginal ultrasound during the following months. The precise localization of the grafted tissue was particularly helpful when its revascularization and functional recovery were followed up using, respectively, colour Doppler and transvaginal follicle growth examination. In conclusion, the use of a slowly reabsorbed, ultrasound-detectable surgical thread as an ultrasound-detectable marker able to improve the localization of the exact site at which ovarian tissue was grafted is proposed.

La crioconservazione del tessuto gonadico femminile

RiassuntoLa crioconservazione del tessuto ovarico è una tecnica innovativa per preservare la fertilità delle giovani pazienti a rischio di insufficienza ovarica a causa di trattamenti oncostatici gonadotossici oppure per cause benigne quali patologie genetiche, autoimmuni od ovariche. Il tessuto ovarico crioconservato, dopo scongelamento, può essere reimpiantato orto elo eterotopicamente oppure posto in coltura per ottenere la maturazione in vitro dei follicoli primordiali. Ad oggi nel mondo sono nati 17 bambini da ritrapianto ortotopico di tessuto ovarico. Il primo e unico caso di bambino nato con questa tecnica in Italia è stato recentemente ottenuto dalla nostra équipe.