Jean Squifflet

Livebirth after orthotopic transplantation of cryopreserved ovarian tissue

BACKGROUNDnThe 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.nnnMETHODSnIn 2003, after freeze-thawing, orthotopic autotransplantation of ovarian cortical tissue was done by laparoscopy.nnnFINDINGSn5 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.nnnINTERPRETATIONnWe 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.

Laparoscopic management of endometriomas using a combined technique of excisional (cystectomy) and ablative surgery

OBJECTIVEnTo describe and evaluate a new technique of laparoscopic treatment of endometriomas that combines excisional and ablative surgery.nnnDESIGNnDescriptive and prospective study.nnnSETTINGnGynecology research unit in a university hospital.nnnPATIENT(S)nFifty-two women under 35 years of age presenting for infertility and/or pelvic pain with endometriomas larger than 3 cm were included in the study. None had undergone any surgery for endometriosis.nnnINTERVENTION(S)nA large part of the endometrioma wall was first excised according to the cystectomy technique. After this first step, CO(2) laser was used to vaporize the remaining 10%-20% of the endometrioma wall close to the hilus.nnnMAIN OUTCOME MEASURE(S)nThe feasibility of this new technique was assessed. Ovarian volume and antral follicle count (AFC) were compared between operated ovaries and nonoperated ovaries of patients with endometriosis and controls (women with male factor infertility).nnnRESULT(S)nThe combined technique was possible in all cases. The volume of the ovary after the combined technique was similar to that of the contralateral normal ovary, as well as to that observed in infertile women without endometriosis presenting for male factor infertility. The AFC on day 2-5 showed the same number of antral follicles in all subgroups. Histopathology of the excised part of the endometrioma revealed the presence of follicles in only one case (2%). The pregnancy rate was 41% at a mean follow-up of 8.3 months. Recurrence of a small endometrioma was observed in only one case (2%).nnnCONCLUSION(S)nThe combined technique (stripping and ablation) has proved not to be deleterious to the ovary.

Bladder endometriosis must be considered as bladder adenomyosis.

OBJECTIVEnTo present data from a series of 17 cases of bladder endometriosis.nnnDESIGNnClinical study.nnnSETTINGnA university hospital department of gynecology.nnnPATIENT(S)nSeventeen patients complaining of menstrual urinary symptoms and/or pelvic pain.nnnINTERVENTION(S)nDiagnosis and resection of a bladder adenomyotic nodule.nnnMAIN OUTCOME MEASURE(S)nHistologic analysis and postsurgical outcome.nnnRESULT(S)nSeventy-six percent of the patients reported menstrual mictalgia and pollakiuria, and 88% reported dysmenorrhea and dyspareunia. Cystoscopy, intravenous pyelography, and magnetic resonance imaging revealed a nodular mass in the anterior fornix adjacent to the uterine wall, developed in the vesical muscularis and involving the vesical mucosa in all cases but one. The bladder nodule was associated with a rectovaginal nodule in six cases (35%). Because recurrence was noted soon after cessation of medical therapy, surgical excision was proposed. The vesical mucosa was found to be intact in almost all cases, so extramucosal laparoscopic excision was the method of choice. Histologic examination proved that 90% of the nodule consisted of smooth muscle hyperplasia.nnnCONCLUSION(S)nSo-called bladder endometriosis is actually an adenomyotic nodule of the bladder which, from a histologic point of view, is similar to a rectovaginal adenomyotic nodule and frequently (35%) associated with it.

Endometriomas as a possible cause of reduced ovarian reserve in women with endometriosis.

OBJECTIVEnTo evaluate the adverse effects of endometriomas on ovarian reserve.nnnDESIGNnAnalysis of prospectively collected biopsy samples.nnnSETTINGnGynecology research unit in a university hospital.nnnPATIENT(S)nWomen younger than age 35 years with endometriomas.nnnINTERVENTION(S)nBiopsy of normal cortex from ovaries affected by endometriomas (≤4 cm) and contralateral ovaries without cysts.nnnMAIN OUTCOME MEASURE(S)nPresence of cortex-specific stroma, observation of superficial endometriosis, follicular density, and presence of fibrosis.nnnRESULT(S)nTwenty samples of cortical tissue from ovaries with endometriomas and 11 from contralateral ovaries without cysts were analyzed. Follicular density was significantly lower in cortex from ovaries with endometriomas than in cortex from contralateral ovaries without cysts (mean ± SD = 6.3 ± 4.1/mm(3) vs 25.1 ± 15.0/mm(3)). Eleven (55%) cortical samples from ovaries with endometriomas showed fibrosis and concomitant loss of cortex-specific stroma, not observed in contralateral normal ovaries. Multivariate analysis revealed that the presence of endometrioma and fibrosis were significantly and independently associated with follicular density.nnnCONCLUSION(S)nEndometriotic cyst formation and associated structural tissue alterations in apparently normal ovarian cortex may be a cause of reduced ovarian reserve. Early diagnosis and intervention may be beneficial in women with endometriomas to protect their ovarian function.

Restoration of ovarian function in orthotopically transplanted cryopreserved ovarian tissue: a pilot experience.

Cryopreservation of ovarian tissue is currently proposed to young cancer patients before chemo- or radiotherapy to preserve their fertility. In this study, ovarian cortex was removed by laparoscopy from five women and cryopreserved before chemotherapy. After chemotherapy, they all experienced amenorrhoea due to premature ovarian failure and requested reimplantation of their cryopreserved ovarian tissue several years later. Thawed fragments were then grafted to an orthotopic site in all five women. Two of them underwent a second reimplantation. Ovarian function recovery was evaluated by hormone concentration measurement, follicular development on ultrasound and menstruation recovery. The first signs of ovarian function restoration (oestradiol peak, decrease in FSH, ultrasound showing follicular development) occurred between 16 and 26 weeks after reimplantation. Elevated FSH concentrations were sometimes observed between series of consecutive ovulatory cycles, demonstrating the presence of a relatively low ovarian reserve. There were no signs of disease recurrence in any patients with malignant disease. In conclusion, restoration of ovarian function was observed in all cases. Grafts remained functional in all the women. Transplantation of cryopreserved ovarian tissue to an orthotopic site appears to restore ovarian endocrine function, without any signs of disease recurrence.

Pregnancy and live birth after autotransplantation of frozen-thawed ovarian tissue in a patient with metastatic disease undergoing chemotherapy and hematopoietic stem cell transplantation

OBJECTIVEnTo report a live birth after orthotopic transplantation of cryopreserved ovarian tissue.nnnDESIGNnCase report.nnnSETTINGnDepartment of Gynecology, Cliniques Universitaires Saint-Luc, Brussels.nnnPATIENT(S)nWoman with metastatic cancer who had her ovarian tissue cryopreserved in 2001 before undergoing chemotherapy and hematopoietic stem cell transplantation, resulting in premature ovarian failure.nnnINTERVENTION(S)nOrthotopic reimplantation of ovarian cortex performed 7 years after cryopreservation.nnnMAIN OUTCOME MEASURE(S)nRestoration of ovarian activity.nnnRESULT(S)nRestoration of ovarian activity was observed 3.5 months after reimplantantation, and ongoing pregnancy was diagnosed 9 months after grafting. The patient delivered a healthy baby weighing 2.830 kg.nnnCONCLUSION(S)nOur patient represents the thirteenth live birth to occur after orthotopic reimplantation of cryopreserved tissue, but the first in a woman treated for metastatic disease.

A review of 15 years of ovarian tissue bank activities

PurposeTo review 15xa0years of activities in ovarian tissue cryobanking from medical database files, including patient indications, histological evaluation and clinical characteristics.MethodsRetrospective longitudinal analysis of data from an ovarian tissue bank in an academic hospital. Five hundred and eighty-two patients had their ovarian tissue cryobanked between April 1997 and January 2012. Analysis of cryobanking database: precryopreservation patient characteristics, indications and safety issues, laboratory files and postcryopreservation clinical data.ResultsOf the 582 patients who had their ovarian tissue cryopreserved, 106 patients donated for research purposes and 476 patients for fertility preservation and long-term cryopreservation. Clinical data analysis of the 476 patients revealed a mean age at the time of cryopreservation of 23u2009±u20098.5xa0years (range: 9xa0months – 39xa0years), with 96.2xa0% of subjects aged ≤35xa0years (nu2009=u2009458). Among 391 cases of malignant disease, hematological malignancies (39.9xa0%, nu2009=u2009156) and breast cancer (21.7xa0%, nu2009=u200985) were the two main indications. At histology, malignant cells were found in ovarian tissue from leukemia patients (nu2009=u20093) and non-Hodgkin’s lymphoma patients (nu2009=u20092). Eleven patients underwent autotransplantation, resulting in 5 live births and 1 ongoing pregnancy.ConclusionThis is the largest and most comprehensive study to describe and analyze indications and clinical patient characteristics before and after ovarian tissue cryopreservation. The procedure is safe, easy and promising. The database concept is a useful tool in patient selection for autotransplantation.

Laparoscopic Repair of Post-Cesarean Section Uterine Scar Defects Diagnosed in Nonpregnant Women

Herein we describe laparoscopic repair of uterine scar defects after cesarean section and pregnancy outcomes in a series of 13 patients. Defects and the residual anterior uterine wall were evaluated using ultrasound and magnetic resonance imaging (MRI). Patients clinical symptoms were recorded. Pregnancy outcomes were investigated after laparoscopic surgical repair. Intervention included laparoscopic repair of the defect, including excision of fibrotic tissue and laparoscopic closure of the anterior uterine wall. The defect was completely corrected using this technique in all 13 patients. Four patients became pregnant spontaneously, 3 delivered via cesarean section between 38 and 39 weeks, and 1 is currently pregnant. Evaluation of uterine scar defects after cesarean section can be performed using ultrasound and MRI, and the defect can be repaired via laparoscopy, with reproducible postoperative anatomic and functional outcomes.

Endometrial laser intrauterine thermotherapy: the first series of 100 patients observed for 1 year

OBJECTIVEnTo describe a new instrument (GyneLase) that offers a new approach (endometrial laser intrauterine thermal therapy [ELITT]) to treatment of menorrhagia and to evaluate the efficacy of ELITT in the management of dysfunctional uterine bleeding.nnnDESIGNnProspective study.nnnSETTINGnUniversity hospital.nnnPATIENT(S)n100 premenopausal women with dysfunctional uterine bleeding were observed for 1 year.nnnINTERVENTION(S)nIntrauterine laser thermotherapy with a diode laser.nnnMAIN OUTCOME MEASUREMENT(S)nAmenorrhea rate after 1 year.nnnRESULT(S)nThe amenorrhea rate after 1 year of follow-up was 71%, and the rate of amenorrhea/severe hypomenorrhea rate was >90%; these rates are much higher than those in the literature after such procedures as electrosurgery or intrauterine thermal balloon therapy. The ELITT procedure is an inherently safe and simple alternative, providing controlled and effective treatment of the entire endometrium. In contrast to traditional endometrial ablation using a neodymium yttrium-aluminum-garnet laser, the ELITT procedure does not require intensive training or hysteroscopic control; it is also far less risky, because the power used per unit area is 1,000 times lower.nnnCONCLUSION(S)nThe ELITT procedure is a new nonhysteroscopic technique for endometrial ablation. The technique is very safe and offers the highest amenorrhea rate to date in the literature.

Live birth after allografting of ovarian cortex between genetically non-identical sisters

Aggressive chemotherapy generally results in the loss of both endocrine and reproductive functions. If the patient has not undergone previous oocyte, embryo or ovarian tissue cryopreservation, orthotopic allotransplantation of fresh ovarian tissue from a genetically non-identical sister may be considered. Here, we describe a case report. The patient, aged 15 years and presenting with homozygous sickle cell anemia, underwent chemotherapy (busulfan, cyclophosphamide) and total body irradiation before bone marrow transplantation, the donor being her HLA-compatible sister. HLA group analysis later revealed complete chimerism. When the patient was 32 years old, ovarian allografting was performed, with the ovarian tissue donor being the same sister who had already donated bone marrow. The goal was to restore ovarian activity and natural fertility. No immunosuppressive therapy was administered. No sign of rejection was observed. Restoration of ovarian function was achieved 3.5 months after transplantation, as proved by the first estradiol peak and follicular development detected by ultrasound. After 9 months of regular ovulatory cycles, IVF was attempted because proximal tubal stenosis (unknown at the time of grafting) could not be repaired by tubal reanastomosis. After stimulation, three oocytes were retrieved. Two embryos were obtained. One embryo was frozen and the other was transferred, resulting in an ongoing pregnancy. The patient delivered a healthy baby girl weighing 3.150 g at 37 2/7 weeks of gestation.