Céline Pirard

Livebirth after orthotopic transplantation of cryopreserved ovarian tissue

BACKGROUND The lifesaving treatment endured by cancer patients leads, in many women, to early menopause and subsequent infertility. In clinical situations for which chemotherapy needs to be started, ovarian tissue cryopreservation looks to be a promising option to restore fertility. In 1997, biopsy samples of ovarian cortex were taken from a woman with stage IV Hodgkins lymphoma and cryopreserved before chemotherapy was initiated. After her cancer treatment, the patient had premature ovarian failure. METHODS In 2003, after freeze-thawing, orthotopic autotransplantation of ovarian cortical tissue was done by laparoscopy. FINDINGS 5 months after reimplantation, basal body temperature, menstrual cycles, vaginal ultrasonography, and hormone concentrations indicated recovery of regular ovulatory cycles. Laparoscopy at 5 months confirmed the ultrasonographic data and showed the presence of a follicle at the site of reimplantation, clearly situated outside the ovaries, both of which appeared atrophic. From 5 to 9 months, the patient had menstrual bleeding and development of a follicle or corpus luteum with every cycle. 11 months after reimplantation, human chorionic gonadotrophin concentrations and vaginal echography confirmed a viable intrauterine pregnancy, which has resulted in a livebirth. INTERPRETATION We have described a livebirth after orthotopic autotransplantation of cryopreserved ovarian tissue. Our findings suggest that cryopreservation of ovarian tissue should be offered to all young women diagnosed with cancer.

Live birth after transplantation of frozen-thawed ovarian tissue after bilateral oophorectomy for benign disease.

OBJECTIVE To report the restoration of ovarian function and pregnancy in a woman after bilateral oophorectomy for benign disease after autotransplantation of cryopreserved ovarian cortex. DESIGN Case report. SETTING Gynecology research unit in a university hospital. PATIENT(S) A 28-year-old woman who underwent bilateral adnexectomy for ovarian abscesses at the age of 18 years. INTERVENTION(S) We performed ovarian cortex autotransplantation to a peritoneal pocket in the broad ligament. MAIN OUTCOME MEASURE(S) Restoration of ovarian activity and pregnancy. RESULT(S) Restoration of ovarian function began at 20 weeks and was achieved 24 weeks after transplantation. After the fifth stimulation attempt, two mature oocytes were obtained and microinjected. One embryo (seven cells) was obtained and transferred, leading to a normal pregnancy. The patient delivered a healthy baby boy weighing 2,370 g at 38 weeks of gestation. CONCLUSION(S) Ovarian cortex cryopreservation can be performed at the time of surgery for benign diseases when fertility is impaired. We report the first pregnancy to occur after ovarian tissue cryopreservation for benign ovarian pathology after bilateral oophorectomy.

Safety of conservative management and fertility outcome in women with borderline tumors of the ovary.

OBJECTIVE To assess the safety of fertility-sparing treatment and the remaining chance of childbearing after surgery. DESIGN Retrospective clinical study. DESIGN Gynecology department of a university teaching hospital. PATIENT(S) Seventy-five women underwent surgical management in our institution between 1986 and 2001 for borderline tumors of the ovary. INTERVENTION(S) Fifty-nine patients were treated by radical, fertility-compromising surgery. The remaining 16 patients underwent conservative surgery, preserving the uterus and at least some functional ovarian tissue. Seven unilateral adnexectomies, one simple cystectomy, and two adnexectomies associated with contralateral cystectomy were performed. MAIN OUTCOME MEASURE(S) Recurrence, survival, and pregnancy rates. RESULT(S) The observed recurrence rates after radical and conservative surgery were 0.0% and 18.7%, respectively. No disease-related deaths occurred in any group; there is no significant difference in survival rates. We can report 12 pregnancies in 7 of 11 women who underwent fertility-sparing management and who wished to become pregnant. CONCLUSION(S) In certain circumstances, conservative management offers a safe solution for borderline tumors of the ovary. Recurrence is noted significantly more often after this type of treatment, but all cases of recurrent disease can be detected with close follow-up and can be treated accordingly. No significant change in survival rates was found. Moreover, the pregnancy rate in women desiring pregnancy, those treated conservatively, was as high as 63.6%.

IVF outcome in patients with orthotopically transplanted ovarian tissue

BACKGROUND Chemo- or radiotherapy can induce premature ovarian failure (POF), and ovarian tissue cryopreservation and transplantation may be proposed to restore ovarian function. Our aim was to evaluate the quality of oocytes and embryos derived from frozen-thawed transplanted ovarian tissue. MATERIALS AND METHODS Women were 21-28 years old at tissue cryopreservation. Nine women suffering POF following chemotherapy with or without radiotherapy underwent orthotopic ovarian tissue transplantation. After 12 months of spontaneous cycles without pregnancy, oocyte retrieval was performed in four patients during mildly stimulated or spontaneous cycles. ICSI was performed in all cases, with embryo transfer on day 3. Light and electron microscopy was used to study oocytes and embryos. RESULTS Signs of ovarian function restoration (estradiol peak, decreased FSH, follicular development) began 16-26 weeks after reimplantation. Twenty-one oocyte retrieval attempts were made. At least one oocyte was collected in 15 cases, giving an empty follicle rate per retrieval of 29% (6/21). Sixteen oocytes were recovered, of which 6 were abnormal or immature (38%) and 10 (62%) were in metaphase II (MII). Three MII oocytes failed to fertilize, two showed abnormal fertilization and five normal MII oocytes successfully fertilized with subsequent normal embryo development (Grade 2), yielding an embryo transfer rate of 24% per retrieval. No pregnancy occurred. CONCLUSIONS IVF in women with orthotopically grafted frozen-thawed ovarian tissue involves a higher risk of empty follicles, abnormal or immature oocytes, and low embryo transfer rates.

Current Thinking on the Pathogenesis of Endometriosis

This manuscript is a review of new ideas regarding the pathogenesis of peritoneal endometriosis, ovarian endometriosis, and retroperitoneal adenomyosis. Peritoneal endometriosis, the different aspects of which (black, red and white) represent distinctive steps in the evolutionary process, can be explained by the transplantation theory. Red lesions are the most active and most highly vascularized lesions and are considered to be the first stage of peritoneal endometriosis. The retroperitoneal nodule is an adenomyotic nodule whose histopathogenesis is not related to the implantation of regurgitated endometrial cells but to metaplasia of Müllerian remnants located in the rectovaginal septum. Metaplastic changes of Müllerian rests into adenomyotic glands involving the rectovaginal septum and the retroperitoneal space are responsible for the striking proliferation of the smooth muscle, creating an adenomyomatous appearance similar to that of adenomyosis in the endometrium.

Cross-border reproductive care in Belgium

BACKGROUND Cross-border reproductive care indicates the cross-border movements made by patients to obtain infertility treatment they cannot obtain at home. The problem at present is that empirical data on the extent of the phenomenon are lacking. This article presents the data on infertility patients going to Belgium for treatment. METHODS A survey was conducted among the centres for reproductive medicine that are allowed to handle oocytes and create embryos (B-centres). Data were collected on the nationality of patients and the type of treatment for which they attended during the period 2000-2007. RESULTS Sixteen of 18 centres responded to the questionnaire. The flow of foreign patients has stabilized since 2006 at approximately 2100 patients per year. The majority of foreign nationals seeking treatment in Belgium were French women for sperm donation. The next highest group was patients entering the country to obtain ICSI with ejaculated sperm. CONCLUSIONS There are clear indications that numerous movements are motivated by the wish to evade legal restrictions in ones home country, either because the technology is prohibited or because the patients have characteristics, which exclude them from treatment in their own countries.

Uterine necrosis and sepsis after vascular embolization and surgical ligation in a patient with postpartum hemorrhage

Because no direct improvement was observed (dramatic decrease in Hb to 3.2 g/dL despite the patient receiving multiple blood transfusions and serious difficulties for the anesthetists in maintaining vital parameters), a decision was made to perform immediate laparotomy for hysterectomy. A median laparotomy was performed. Ligation of the uterine and utero-ovarian arteries and endo-uterine exploration were performed. The hemorrhage was then stopped.

The efficacy of medical and surgical treatment of endometriosis-associated infertility and pelvic pain.

This article is a review of the efficacy of medical and surgical treatment of endometriosis-associated infertility and pelvic pain. Endometriosis is the cause of pelvic pain (dysmenorrhea, dyspareunia) and infertility in more than 35% of women of reproductive age. Complete resolution of endometriosis is not yet possible but therapy has essentially three main objectives: (1) to reduce pain; (2) to increase the possibility of pregnancy; (3) to delay recurrence for as long as possible. It could be concluded that a consensus will probably never be reached on minimal and mild endometriosis. Nevertheless, because the Canadian study reported a large number of cases, we strongly support the view that visible endometriosis must be removed at the time of surgery. In cases of moderate and severe endometriosis-associated infertility, the combined approach (operative laparoscopy with GnRH-a) must be considered as ‘first-line’ treatment. The mean pregnancy rate of 50% reported in the literature following surgery provides scientific proof that operative treatment should be undertaken first to give our patients the best chance of conceiving naturally.

Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a randomized study.

This randomized controlled study compared the effectiveness of a gonadotrophin releasing hormone (GnRH) antagonist protocol with or without oral contraceptive (OC) pretreatment on the number of oocytes retrieved in IVF or intracytoplasmic sperm injection (ICSI) patients. Sixty-four patients were randomized to start recombinant human FSH (r-hFSH) on day 2 or 3 after OC withdrawal (OC group) or on day 2 of a natural cycle (control group). From stimulation day 6 onwards, all patients were treated with daily (0.5 mg/ml) GnRH antagonist (Antide). OC pretreatment resulted in significantly lower starting concentrations of FSH, LH and oestradiol (P < 0.001) and a thinner endometrium (P < 0.0001). In the early stimulation period, fewer large follicles were found after OC pretreatment, leading to a significantly extended stimulation period (11.6 versus 8.7 days, P < 0.0001) with more follicles on the day of recombinant human chorionic gonadotrophin administration (15.4 versus 12.5, P = 0.02) and more oocytes retrieved (13.5 versus 10.2, P < 0.001) as compared with the control group. GnRH antagonist regimen, pretreated with OC, prevented the early endogenous FSH rise and improved follicular homogeneity, resulting in more oocytes. As a consequence of the extended treatment period, more rhFSH was required.

Contribution to More Patient-Friendly ART Treatment: Efficacy of Continuous Low-Dose GnRH Agonist as the Only Luteal Support—Results of a Prospective, Randomized, Comparative Study

Background. The aim of this pilot study was to evaluate intranasal buserelin for luteal phase support and compare its efficacy with standard vaginal progesterone in IVF/ICSI antagonist cycles. Methods. This is a prospective, randomized, open, parallel group study. Forty patients underwent ovarian hyperstimulation with human menopausal gonadotropin under pituitary inhibition with gonadotropin-releasing hormone antagonist, while ovulation trigger and luteal support were achieved using intranasal GnRH agonist (group A). Twenty patients had their cycle downregulated with buserelin and stimulated with hMG, while ovulation trigger was achieved using 10,000 IU human chorionic gonadotropin with luteal support by intravaginal progesterone (group B). Results. No difference was observed in estradiol levels. Progesterone levels on day 5 were significantly lower in group A. However, significantly higher levels of luteinizing hormone were observed in group A during the entire luteal phase. Pregnancy rates (31.4% versus 22.2%), implantation rates (22% versus 15.4%), and clinical pregnancy rates (25.7% versus 16.7%) were not statistically different between groups, although a trend towards higher rates was observed in group A. No luteal phase lasting less than 10 days was recorded in either group. Conclusion. Intranasal administration of buserelin is effective for providing luteal phase support in IVF/ICSI antagonist protocols.