J.G. Schenker

A laparoscopic technique for obtaining ovarian cortical biopsy specimens for fertility conservation in patients with cancer

OBJECTIVE To evaluate the efficacy of a newly designed round biopter as a practical and safe method for collecting ovarian tissue for cryopreservation in young women with cancer before chemotherapy. DESIGN Prospective study of young women volunteering for research (Leeds, United Kingdom) and patients with cancer (Jerusalem, Israel and Leeds, United Kingdom) undergoing laparoscopic ovarian cortical tissue biopsy and cryopreservation before administration of high-dose radiochemotherapy. SETTING Two university-based tertiary referral centers of oncology and gynecology (Hadassah Medical Center, Israel; Leeds General Infirmary, United Kingdom). PATIENT(S) Twenty female volunteers undergoing routine laparoscopic gynecologic procedures (age, 25-34 years) and 20 young women (age, 11-30 years) with advanced cancer requiring potentially sterilizing radiochemotherapy. INTERVENTION(S) Cortical ovarian tissue biopsies performed under laparoscopy with use of the round biopter. RESULT(S) The laparoscopic sampling procedure was uncomplicated in all cases. In treated patients, five to six samples were obtained (5 mm in diameter; 2-3 mm in depth) using the round biopter, and radiochemotherapy was administered without delay. In volunteers, no adhesions were noted at repeat laparoscopy (9 patients). All biopsy specimens were cryopreserved, and histologic examination confirmed the presence of many primordial follicles. CONCLUSION(S) Laparoscopic ovarian biopsy performed with the round biopter is a safe and efficient method for collecting ovarian tissue for cryopreservation in patients with cancer.

Surgical treatment of vulvar lichen sclerosus: a review.

Surgical therapy of lichen sclerosus of the vulva consists of three main operations: vulvectomy (with or without a skin graft), cryosurgery, and laser ablation. It is indicated in two conditions, either when malignant transformation is present or is likely to occur, or when medical treatment has failed. The overall risk for malignant transformation of vulvar lichen sclerosus is low, ranging between 0 and 9 percent. However, specific histological criteria, such as mixed dystrophy, have recently been associated with higher malignancy rates. Vulvectomy is indicated only when these criteria are met. Both skinning and simple vulvectomies are associated with recurrence rates as high as 50 percent. However, better sexual function and cosmetic results have been reported in the former, especially with concomitant split skin grafting. Cryosurgery also has high recurrence rates, although short-term results are favorable. Although only small series have been reported, laser therapy seems to carry better long-term results than other modes of treatment. Convalescence is complete within 6 weeks posttreatment, and remission rates are as high as 85 percent at 3 years of follow-up. The high recurrence rate of all surgical modalities makes surgical treatment suitable only for patients who failed to respond to multiple medical treatments such as topical high potent steroid ointments, testosterone, and retinoids.

Serum copper and zinc levels in patients taking oral contraceptives.

Serum copper and zinc levels of 251 healthy women aged 19-30 years taking various combined and sequential oral contraceptives (OCs) were compared with those of 91 healthy women not taking OCs. Average serum copper level for the OC group was significantly greater than that of controls and serum zinc level was significantly lower than that of controls the respective changes exceeding normal ranges in 21 of the women. Length of OC intake type and composition of OC and day of cycle had no significant effect on copper level but zinc level was lower in those taking sequential compounds. Serum metal levels may eventually play a role in determining patient selection or rejection for OC therapy.

Umbilical cord blood for use in transplantation

Bone marrow transplantation has rapidly progressed over the last two decades offering cure and prolonged disease-free survival for patients suffering from certain hemato-oncological malignancies or metabolic disorders. However, bone marrow transplantation is limited by the paucity of major histocompatibility loci antigen (HLA)-matched donors, and the morbidity and mortality due to graft-versus-host disease. Recently it has been shown, that umbilical cord blood represents a unique source of transplantable hematopoietic progenitor cells. Currently, human umbilical cord blood from a newborn sibling has been used successfully for hematopoietic reconstitution of approximately 40 children with congenital or malignant diseases. Establishment of umbilical cord blood banks might alleviate some of the problems associated with bone marrow transplantation. The developments in this field which have occurred during the last decade, as well as the importance of cooperation between the obstetric and transplantation staff, are discussed in this review. Certain ethical problems remain surrounding the issue of using human umbilical cord blood for allogeneic transplantation which must be addressed.

Exaggerated Prolactin Response to Thyrotropin-Releasing Hormone and Metoclopramide in Primary Testicular Failure*

Twenty-eight severely oligospermic and azoospermic men aged 20 to 42 years were challenged with luteinizing hormone (LH)-releasing hormone (LHRH), thyrotrophin-releasing hormone (TRH), and the dopaminergic antagonist, metoclopramide, given at 30-minute intervals. According to basal gonadotropin levels, the patients were subdivided into three groups: those with severe testicular failure (basal LH > 20 mIU/ml and FSH > 14 mIU/ml); those with moderate testicular failure with predominant seminiferous tubule involvement (LH < 20 mIU/ml and FSH > 14 mIU/ml) and those with mild testicular failure (LH < 20 mIU/ml and FSH < 14 mIU/ml. With one exception, mean basal prolactin (PRL) levels were normal in all patients. In all three groups, however, there was an exaggerated PRL response to TRH, the response in severe and moderate testicular failure being greater than that in mild testicular failure. The response to metoclopramide was increased only in the first two groups, not in the group with mild testicular failure. When individual patients and control subjects were considered together, the peak PRL response to TRH correlated with both basal and peak gonadotropin responses to LHRH. However, the PRL responses did not correlate with 17 beta-estradiol, estrone, testosterone, or the estradiol-testosterone ratio. It is concluded that oligospermic and azoospermic subjects with the most severe testicular failure and the highest gonadotropin levels have the greatest PRL increases after TRH and metoclopramide, indicating that the PRL response is related to the degree of testicular failure.

Prolactin response to metoclopramide and chlorpromazine in primary testicular failure and isolated gonadotrophin deficiency.

The aim of the present study was to measure the PRL response to metoclopramide (MET) and chlorpromazine (CPZ) in seventeen patients with primary testicular failure and eight patients with isolated gonadotrophin deficiency (IGD). The responses were compared with those to TRH. Basal gonadotrophins and peak responses to LHRH were increased in testicular failure and reduced in IGD. Basal PRL levels were normal in both groups of patients. However, when compared with controls, the PRL response to both MET and CPZ as well as to TRH was exaggerated in primary testicular failure, whereas the responses were decreased in IGD. In both patient groups, as well as in the controls, the PRL response to MET exceeded that to TRH and CPZ. It is suggested that alterations in the steroid milieu are responsible for the exaggerated PRL response to MET, CPZ and TRH in primary testicular failure and the reduced response observed in IGD.

Insulin Resistant and Nonresistant Polycystic Ovary Syndrome Represent Two Clinical and Endocrinological Subgroups

We studied the clinical and endocrine features of 35 patients with polycystic ovary syndrome (PCOS) who are either insulin resistant or non-insulin resistant. The occurrence of insulin resistance was determined by measuring insulin and glucose concentrations following a standard 75 g oral glucose load. All patients were evaluated by anthropometric measurements: body mass index (BMI), percentage of body fat (BCF) and waist-to-hip ratio (W/H), degree of hirsutism (Ferriman-Gallwey method) and endocrine profile. Fourteen patients had insulin resistance of unknown origin whereas four were due to a type A insulin receptor mutation, and 17 were non-insulin resistant. The insulin resistant patients were significantly more obese (higher BMI P < 0.0001, BCF P < 0.002 and W/H ratio P < 0.005) and were more hirsute (P < 0.002) than the non-insulin resistant patients. Testosterone concentrations were significantly higher in the insulin resistant group than in the non-insulin resistant group (2.65 versus 1.37 nmol/l; P < 0.027), whereas sex hormone-binding globulin was lower in insulin resistant patients (30.61 versus 19.48 nmol/l; P < 0.02). Non-insulin resistant patients showed a high luteinizing hormone to follicle stimulating hormone ratio, while a normal ratio was found in the insulin resistant subpopulation (2.94 versus 1.34; P < 0.0001). We concluded that PCOS comprises two subpopulations, one with insulin resistance of different aetiologies and the other which has no insulin resistance. These two groups differ in their anthropometric and endocrine features. The diagnosis of insulin resistance in PCOS can be easily determined by the insulin response to an oral glucose tolerance test.

CLOMIPHENE CITRATE DOES NOT MODIFY THE EXAGGERATED THYROTROPHIN RESPONSE TO THYROTROPHIN-RELEASING HORMONE OCCURRING IN PRIMARY TESTICULAR FAILURE

Patients with primary testicular failure have increased basal TSH levels and an exaggerated TSH response to TRH in the presence of normal circulating levels of thyroid hormones. In order to evaluate if this TSH profile is an oestrogenrelated phenomenon, sixteen patients with primary testicular failure were challenged with 200 μg TRH prior to and after the administration of clomiphene citrate. The latter was given in a dose of 100 mg/day for 4 weeks to ten patients; 200 mg/day for 4 weeks to three patients and 100 mg/day for 2 months to the final three patients.