Pieces of ovarian cortical tissue (0.3-2 mm in diameter) were obtained during gynaecological operations by biopsy or as a result of oophorectomy from 19 women aged 19-44 years. The tissue was frozen in a programmable freezer using one of two different cryoprotectants, either 1.5 M dimethylsulphoxide (DMSO), or a combination of 1,2-propanediol (1.5 M) and sucrose (0.1 M). After cryopreservation lasting from 24 h to 5 weeks, the ovarian pieces were thawed and studied histologically. Specimens taken before and after cryopreservation with either protectant showed no signs of tissue necrosis. Follicles at similar developmental stages were found before and after freezing. The proportions of follicles showing signs of atresia, 27% in the non-frozen tissue and 19% in the frozen-thawed tissue, were not significantly different. Oocytes, too, had the same appearance after freezing and thawing with both cryoprotectants as was seen in the specimens taken before freezing. These results suggest that cryopreservation of human ovarian tissue is feasible. However, the normality of the oocytes taken from tissue which has been frozen still needs to be established. Cryopreservation of ovarian tissue would be potentially an excellent method for storage of human oocytes once methods for their maturation in vitro have been developed.
The study tests the hypothesis that small ovaries measured on transvaginal sonography (TVS) are associated with a poor response to ovulation induction by human menopausal gonadotrophin (HMG) for in-vitro fertilization (IVF). A total of 140 infertile patients with morphologically normal ovaries undergoing IVF was studied. The mean ovarian volume of each patient was measured on TVS before starting HMG. Subsequent routine IVF management was conducted without knowledge of the results of TVS. The mean ovarian volume was 6.3 cm3 (range 0.5-18.9, SD= 3.1). Patients (n = 17; group A) with small ovaries of < 3 cm3 (i.e. overall mean volume - 1 SD) were compared to patients (n = 123; group B) with ovaries > or = 3 cm3. Both groups were of similar age (mean 35.8 versus 34.4 years). Early basal FSH concentrations were increased in group A (9.5 versus 7.0 mIU/ml, P = 0.025). The cycle was abandoned before planned oocyte recovery in nine patients (52.8%) from group A and in 11 patients (8.9%) from group B because of poor response to ovulation induction (P < 0.001). Increased age and ovarian volume were associated independently with cancellation of the cycles. The remaining eight patients from group A who had oocytes retrieved required higher doses of HMG (87.5 versus 53.8 ampoules, P < 0.01), yielded fewer follicles (10.3 versus 14.5, P < 0.05) and fewer oocytes were recovered from them (6.8 versus 11.0, P < 0.05) compared with group B. There was no difference in the fertilization or pregnancy rates or the number of embryos available for transfer in either group. Our results indicate a strong association between ovarian volume and ovarian reserve. Small ovaries are associated with poor response to HMG and a very high cancellation rate during IVF. Assessment of ovarian size should be an integral part of infertility evaluation.
The improved survival in recent years of young males suffering from cancer, and an understanding of the gonadotoxic effects of chemotherapy treatment, have motivated patients and clinicians to preserve fertility potential before embarking on adjuvant therapy. Among 231 men (mean age 28.0; range 15-56 years) diagnosed with malignant disease and referred to our unit for semen cryopreservation, 112 patients (49.8%) had reduced sperm quality of <10 x 10(6) motile spermatozoa per ejaculate; however, most had sufficient suitable spermatozoa for freezing. In 40 patients (17.3 %) the semen samples were not frozen because of complete azoospermia (n = 32) or only immotile sperm in the ejaculate (n = 2), while six men were unable to produce a single sample. Some 79 men had testicular tumours (group I), 121 suffered from haematological malignancy (leukaemia or lymphoma; group II), and 27 had cancer of different causes (group III). Men in group I had significantly lower (P < 0.001) sperm quality compared with groups II and III. There was no difference between patients with seminoma and non-seminoma tumours. In the haematological malignancy group there was no difference in sperm parameters between leukaemia (n = 12) and lymphoma (n = 77) patients, but patients with Hodgkin's lymphoma had significantly lower sperm quality compared with non-Hodgkin's lymphoma. Following chemotherapy, six couples attended the clinic for assisted conception treatment using the frozen semen. Two had successful intrauterine insemination cycles which each resulted in delivery of a healthy girl; one couple had conceived in their first in-vitro fertilization (IVF) attempt, followed by delivery of healthy twins. Two women conceived after intracytoplasmic sperm injection treatment and the sixth woman achieved only biochemical pregnancy after numerous IVF and frozen embryo replacement cycles. We recommend that a properly designed programme for semen cryopreservation for cancer patients should be developed in leading tertiary assisted conception centres, which have adequate facilities and experience for cryopreservation and can offer the whole range of appropriate assisted reproductive treatment and counselling.
The ageing ovary appears to be characterized by depletion of primordial follicles. The relationship between infertility and the number of follicles in the ovarian cortex is not known. Moreover, there are no accurate markers or clinical methods to predict the decline in ovarian reserve. This study investigates the correlation between early follicular follicle stimulating hormone, ovarian size and follicular density in 60 infertile women aged 19-45 years (mean = 34.4 +/- 5.5). An ovarian biopsy was taken from each patient while performing diagnostic laparoscopy (n = 28) or laparotomy for tubal surgery or myomectomy (n = 32). The median number of follicles was similar in tubal and unexplained infertility patients (9.5 versus 5.5). Increasing age showed a significant negative correlation with follicular density and ovarian volume (r = -0.46, P = 0.0003;. r = -0.43, P = 0.0016, respectively). In women > or = 35 years of age the ovarian volume showed a strong correlation with follicular density (r = 0.71, P < 0.0001). Our results indicate that infertile women in their late thirties and over have a decreased ovarian reserve which could possibly be predicted by ovarian volume measurement. Ovarian biopsy may have a place as part of infertility evaluation in older women.
In recent years, the survival of young males suffering from cancer has been improved. Development of new techniques such as IVF and intracytoplasmic sperm injection enables even low quality spermatozoa to be used successfully. It is possible therefore to preserve fertility potential of cancer patients before embarking on adjuvant chemotherapy and radiotherapy. Recognizing the importance of protecting the fertility potential of these young males, we present our recommendations for sperm cryopreservation based on the 11 year experience of Bourn Hall and the British Joint Council for Clinical Oncology consultation report. This paper discusses the options available for patients who recover from cancer to become fathers. In many cases patients are concerned about possible abnormalities and teratogenic risks to their future children who have been conceived naturally or by fertility treatment. The data available in the literature may reassure the medical community that there is no such increased risk. However, due to the relatively small number of children born after such treatment, a long-term follow-up is required. There is an ongoing debate regarding the justification for the programme due to the small number of patients who make use of their banked spermatozoa. The authors believe in the importance of protecting the fertility potential of cancer patients, enabling them to father their genetic children in the future while fighting their illness.
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