Ninety-five orthotopic transplantations in 74 women of ovarian tissue after cytotoxic treatment in a fertility preservation network: tissue activity, pregnancy and delivery rates.

STUDY QUESTION: What is the success rate in terms of ovarian activity (menstrual cycles) as well as pregnancy and delivery rates 1 year after orthotopic ovarian transplantations conducted in a three-country network? SUMMARY ANSWER: In 49 women with a follow-up >1 year after transplantation, the ovaries were active in 67% of cases and the pregnancy and delivery rates were 33 and 25%, respectively. WHAT IS KNOWN ALREADY: Cryopreservation of ovarian tissue in advance of cytotoxic therapies and later transplantation of the tissue is being performed increasingly often, and the total success rates in terms of pregnancy and delivery have been described in case series. However, published case series have not allowed either a more detailed analysis of patients with premature ovarian insufficiency (POI) or calculation of success rates based on the parameter 'tissue activity'. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of 95 orthotopic transplantations in 74 patients who had been treated for cancer, performed in the FertiPROTEKT network from 2008 to June 2015. Of those 95 transplantations, a first subgroup (Subgroup 1) was defined for further analysis, including 49 women with a follow-up period >1 year after transplantation. Of those 49 women, a second subgroup (Subgroup 5) was further analysed, including 40 women who were transplanted for the first time and who were diagnosed with POI before transplantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Transplantation was performed in 16 centres and data were transferred to the FertiPROTEKT registry. The transplantations were carried out after oncological treatment had been completed and after a remission period of at least 2 years. Tissue was transplanted orthotopically, either into or onto the residual ovaries or into a pelvic peritoneal pocket. The success rates were defined as tissue activity (menstrual cycles) after 1 year (primary outcome) and as pregnancies and deliveries achieved. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of all transplanted 74 women was 31 ± 5.9 years at the time of cryopreservation and 35 ± 5.2 at the time of transplantation. Twenty-one pregnancies and 17 deliveries were recorded. In Subgroup 1, tissue was cryopreserved at the age of 30 ± 5.6 and transplanted at 34 ± 4.9 years. Ovaries remained active 1 year after transplantation in 67% of cases (n = 33/49), the pregnancy rate was 33% (n = 16/49) and the delivery rate was 25% (n = 12/49). In Subgroup 5, tissue was cryopreserved at the age 30 ± 5.9 years and transplanted at 34 ± 5.2 years. Ovaries remained active 1 year after transplantation in 63% of cases (n = 25/40), the pregnancy rate was 28% (n = 11/40) and the delivery rate was 23% (n = 9/40). The success rates were age dependant with higher success in women who cryopreserved at a younger age. In Subgroup 5, tissue was exclusively transplanted into the ovary in 10% (n = 4/40) of women and into a peritoneal pocket in 75% (n = 30/40), resulting in spontaneous conceptions in 91% of patients (n = 10/11). LIMITATIONS, REASONS FOR CAUTION: The data were drawn from a retrospective analysis. The cryopreservation and transplantation techniques used have changed during the study period. The tissue was stored in many tissue banks and many surgeons were involved, leading to heterogeneity of the procedures. However, this does reflect the realistic situation in many countries. Although patients with POI were evaluated before transplantation to allow specific analysis of the transplanted tissue itself, the possibility cannot be excluded that residual ovarian tissue was also reactivated. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest case series worldwide to date and it confirms that cryopreservation and transplantation of ovarian tissue can be a successful option for preserving fertility. Persistent tissue activity 12 months after transplantation suggests that the pregnancy and delivery rates may increase further in the future. As transplantation into the peritoneum results in a high success rate, this approach may be an alternative to transplantation into the ovary. However, in order to establish the best transplantation site, a randomized study is required. STUDY FUNDING/COMPETING INTEREST: This study was in part funded from the Deutsche Forschungsgemeinschaft (# DI 1525) and the Wilhelm Sander Foundation (2012.127.1) and did not receive any funding from a commercial company. No competing interests. TRIAL REGISTRATION NUMBER: None.

Transitional cell carcinoma of the vagina with pagetoid spread pattern.

A distinctive variant of a papillary noninvasive transitional cell carcinoma (TCC) of the vagina removed from a postmenopausal woman is described. The neoplasm was evaluated by immunohistochemistry. The designation of this neoplasm as a TCC is supported by its morphological features and its coexpression for cytokeratin (CK) 7 and CK 20. Its main feature is pagetoid infiltration into adjacent vaginal epithelium. This is the second reported case involving a transitional cell metaplasia (TCM) of the vagina, a possible precursor lesion of the TCC.

Prevention of postoperative thromboembolism by dextran 70 or low-dose heparin.

The efficacy of intravenous infusion of dextran 70 or subcutaneous administration of low-dose heparin in preventing postoperative thromboembolic complications has been investigated in a prospective randomized trial. During part 1 of the study, 232 patients over the age of 40 years who were undergoing major gynecologic surgery underwent a complete test protocol. The 125I fibrinogen uptake test (FUT) was used for the diagnosis of deep vein thrombosis (DVT) in 117 patients in the dextran and 115 patients in the heparin group. Heparin was significantly more effective than dextran for reducing DVT (P less than .001). During part 2 of the study no FUT was done but the incidence of clinical and fatal pulmonary embolism (PE) and the number of complications were studied. Of 444 patients (parts 1 and 2) 1 fatal and 2 nonfatal pulmonary emboli were diagnosed. All the emboli occurred in the dextran group. The benefit: hazard ratio appeared to favor heparin for the prophylaxis of DVT.

[Evaluation of bloody nipple discharge]. / Abklärung einer blutigen Mamillensekretion.

A 64-year old woman was referred for radiological evaluation of right sided bloody nipple discharge lasting for five months. Finally galactography supposed the diagnosis of an intraductal papilloma which was confirmed by surgery. Histopathologically an eight millimeter measuring intraductal papilloma with atypical ductal hyperplasia with signs of a carcinoma in situ was seen.

[Microsurgery of the fallopian tube]. / Mikrochirurgie am Eileiter.

The goal of infertility surgery is to restore anatomic relationship to as close to normal as possible maximizing the chances for conception and intrauterine pregnancy. The outcome has been markedly, improved by the advent of microsurgical techniques. More than 10 years of microsurgical experience have enabled us to clearly define situations where infertility surgery is especially successful. In refertilization after tubal sterilization, the results with microsurgery are unsurpassed. In proximal, but also distal, postinfectious tubal disease, intrauterine pregnancy rates are clearly better than those achieved with in vitro fertilization or other techniques.

Modern synthetic suture materials and abdominal wound closure techniques in gynaecological surgery.

The introduction of modern synthetic suture materials and an individualized approach to wound closure techniques in gynaecological surgery has created new options. Although many issues remain open to question, we have no doubt that catgut and chromic catgut can be declared obsolete in gynaecological surgery. The choice of synthetic suture materials has to be made on personal preferences and clinical experience. If the use of non-absorbable sutures is desired, with few exceptions monofilament suture material is clearly the first choice. Abdominal opening and closure techniques and the selection of appropriate suture materials have to be considered as important factors in minimizing wound healing complications. The decision-making process is based on the knowledge of anatomy, wound healing and possible risk factors. From theoretical considerations, mass closure of all layers apart from skin is considered to be the superior concept. The incidence of incisional hernias and sinus formation will depend on proper technique and possibly the choice of suture material. Some suggestions to individualize opening and closure of the abdomen are made although prospective randomized trials in gynaecology have not yet been performed.

[Myocardial infarction in pregnancy]. / Der Myokardinfarkt in der Schwangerschaft.

Myocardial infarction during pregnancy and puerperium is very rare. Increased awareness of its possible occurrence is important for diagnosis. We report on a 37-year-old woman without coronary risk factors who suffered an anterior septal infarction in the last trimester. Coronary angiography one month after normal delivery and two months after infarction revealed normal coronary arteries. Ventriculography showed anteroseptal akinesia. The assumed etiology of myocardial infarction appears to be coronary spasm. A history of vasospasm in other vascular beds, migraine and Raynaud's phenomenon support this hypothesis. The literature is reviewed with special emphasis on clinical picture, prognosis, etiology and management of myocardial infarction during pregnancy.

[End-to-end anastomosis in the primary repair of anal sphincter laceration occurring during delivery]. / Suffizienz der End-zu-Endanastomose bei primärer Versorgung eines geburtstraumatischen Analsphinkterrisses.

PURPOSE: To assess the quality of end-to-end anastomosis in the primary repair of anal sphincter laceration occurring during delivery. METHODS: Forty-nine women with third degree perineal laceration (PL III) and 42 controls were included in a 3-year postpartal follow-up study. RESULTS: Ultrasound showed end-to-end anastomosis to be inadequate in 22 (48.1 %) women. Thirty-one (63.2 %) women developed grade I-III anal incontinence. DISCUSSION: There was no correlation between ultrasound findings and the presence of anal incontinence. The unsatisfactory sonomorphometric outcome after 6 weeks results from inadequate repair with retraction of the sphincter ends. Defects newly demonstrated after 36 months indicate dedifferentiating atrophy with damage to peripheral motor nerves.

Are cumulus cells necessary for the spontaneous maturation of germinal vesicle-stage oocytes to metaphase II.

PURPOSE: In this study we investigated the need of the support from cumulus cells for germinal-vesicle (GV) oocytes collected from stimulated ovaries to complete their maturation to metaphase II (MII). METHODS: We compared the maturation rate of GV oocytes after coculture with cumulus cells (study group) with their spontaneous maturation in culture medium alone (control group). RESULTS: Sixty-four and nine-tenths percent of the GV oocytes matured to metaphase II in the coculture group, and of these, 43.5% gave normal 2pn zygotes following intracytoplasmic sperm injection (ICSI), while 73.8% of the GV oocytes spontaneously matured to the MII stage and 30% of these reached the zygote stage after ICSI. CONCLUSIONS: It is probable that a follicular factor is responsible for this arrested maturation in the human and that maturation occurs spontaneously when the oocytes are separated from their follicular fluid environment after collection.

Dihydroergotamine and heparin or heparin alone for the prevention of postoperative thromboembolism in gynecology.

The efficacy of combined dihydroergotamine and heparin (DHE-heparin) medication (2500 IU sodium heparin and 0.5 mg DHE, both given subcutaneously twice daily) or low doses of heparin (5,000 IU of sodium heparin given subcutaneously thrice daily) in preventing postoperative thromboembolic complications was investigated in a prospective, randomized trial in 125 patients over the age of 40 years undergoing elective major gynecological surgery. The I125-fibrinogen uptake test was used for the diagnosis of deep vein thrombosis. There was no statistically significant difference in the incidence of thromboembolism between the groups. Major bleeding occurred less often (p < 0.05) in the DHE-heparin group.

Intracytoplasmic sperm injection (ICSI) with testicular sperm extraction (TESE) in non-obstructive azoospermia--two case reports.

Intracytoplasmic sperm injection (ICSI) with microsurgical epididymal sperm extraction (MESA) or testicular sperm extraction (TESE) can be offered to azoospermic men. We report our initial experience of two cases with ICSI-TESE in non-obstructive azoospermia. Both couples had a successful ICSI with embryo transfer. An ongoing triplet pregnancy at 21 weeks is observed.