Newsletter

Table of Contents

20.11.2006

Newsletter No. 6/2006

Reproductive Medicine

Small intramural fibroids and assisted reproduction.
Ovarian failure after laparoscopic excision of bilateral endometriomas

Antiaging

DHEA in elderly women and DHEA or testosterone in elderly men.

Oncology and Reproduction

Prevention of gonadal toxicity and preservation of gonadal function
Ovarian cryopreservation: a review

1. Small intramural fibroids and assisted reproduction.

BACKGROUND: This study aimed to evaluate the effect of small intramural fibroids on the cumulative pregnancy, ongoing pregnancy, live birth and implantation rates after three IVF/ICSI attempts.
METHODS: The first three treatment cycles of women enrolled for IVF/ICSI over a 12-month period were analysed. Only patients with small (< or = 5 cm) intramural fibroids not encroaching upon the endometrial cavity were included in the fibroid group. Cox's hazards regression was used to estimate the hazard ratio (HR) associated with the presence of intramural fibroids. RESULTS: During the study period, 322 women without fibroids (control group) and 112 women with fibroids (study group) underwent 606 IVF/ICSI cycles. The pregnancy, ongoing pregnancy and live birth rates in the study group were 23.6, 18.8 and 14.8% compared with 32.9, 28.5 and 24% in the control group, respectively (P<0.05). Cox regression analysis showed that the pregnancy rate at each cycle was reduced by 39% (HR=0.61, 95% CI=0.39-0.95, P=0.029) in the study group compared with the control group. The cumulative ongoing pregnancy rate was reduced by 43% (HR=0.57, 95% CI=0.35-0.91, P=0.018), and the cumulative live birth rate was reduced by 47% (HR=0.53, 95% CI=0.32-0.87, P=0.013) in the study group. After adjusting for confounding variables, the presence of fibroids was found to significantly reduce the ongoing pregnancy rate at each cycle of IVF/ICSI by 40% (HR=0.60, 95% CI=0.36-0.99, P=0.048) and the live birth rate at each cycle by 45% (HR=0.55, 95% CI=0.32-0.95, P=0.03).
CONCLUSION: Small intramural fibroids are associated with a significant reduction in the cumulative pregnancy, ongoing pregnancy and live birth rates after three IVF/ICSI cycles.

Khalaf Y, Ross C, El-Toukhy T, Hart R, Seed P, Braude P. The effect of small intramural uterine fibroids on the cumulative outcome of assisted conception. Hum Reprod. 2006 Oct;21(10):2640-4. Epub 2006 Jun 21.

2. Ovarian failure after laparoscopic excision of bilateral endometriomas.

OBJECTIVE: This study was undertaken to determine the frequency of postsurgical ovarian failure in patients undergoing laparoscopic excision of bilateral endometriomas.
STUDY DESIGN: Patients who had been operated on for bilateral ovarian endometriosis between January 1995 and December 2003 and who were younger than 40 years at the time of surgery were contacted by telephone and interviewed.
RESULTS: A total of 126 patients were recruited. Mean +/- SD age of patients at the time of surgery was 30.4 +/- 4.3 years. Postsurgical ovarian failure was documented in 3 cases, corresponding to a rate of 2.4% (95% CI 0.5%-6.8%). In all cases, this complication occurred immediately after surgery.
CONCLUSION: Patients who had been operated on for bilateral endometriomas have a low but definite risk of premature ovarian failure occurring immediately after surgery.

Busacca M, Riparini J, Somigliana E, Oggioni G, Izzo S, Vignali M, Candiani M. Postsurgical ovarian failure after laparoscopic excision of bilateral endometriomas. Am J Obstet Gynecol. 2006 Aug;195(2):421-5. Epub 2006 May 8.

3. DHEA in elderly women and DHEA or testosterone in elderly men.

BACKGROUND: Dehydroepiandrosterone (DHEA) and testosterone are widely promoted as antiaging supplements, but the long-term benefits, as compared with potential harm, are unknown.
METHODS: We performed a 2-year, placebo-controlled, randomized, double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo. Among the women, 27 received DHEA and 30 received placebo. Outcome measures included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life.
RESULTS: As compared with the change from baseline to 24 months in the placebo group, subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter (9.2 micromol per liter) in men and by 3.8 microg per milliliter (10.3 micromol per liter) in women. Among men who received testosterone, the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter (1.1 nmol per liter), as compared with the change in the placebo group. A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute, muscle strength, or insulin sensitivity. Men who received testosterone had a slight increase in fat-free mass, and men in both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultradistal radius. Neither treatment improved the quality of life or had major adverse effects.
CONCLUSIONS: Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. (ClinicalTrials.gov number, NCT00254371 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.

Nair KS, Rizza RA, O'Brien P, Dhatariya K, Short KR, Nehra A, Vittone JL, Klee GG, Basu A, Basu R, Cobelli C, Toffolo G, Dalla Man C, Tindall DJ, Melton LJ 3rd, Smith GE, Khosla S, Jensen MD. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. 2006 Oct 19;355(16):1647-59.

4. Prevention of gonadal toxicity and preservation of gonadal function and fertility in young women with systemic lupus erythematosus treated by cyclophosphamide: the PREGO-Study.

BACKGROUND: With dramatically improved survival rates of SLE patients, comorbidity and long-term damage such as premature ovarian failure (POF) gain increasing importance. In the Erlangen cohort, 14% of cyclophosphamide treated patients younger than 41 years have POF, which is a common consequence of cyclophosphamide treatment.
PATIENTS AND METHODS: We tested the concentrations of FSH and LH, before, during and after cyclophosphamide treatment in 63 premenopausal women with SLE without ovarian protection and initiated the PREGO-Study (Prospective randomized study on protection against gonadal toxicity) in patients with SLE.
RESULTS: In lupus patients treated with cyclophosphamide, 60% suffered from POF and hypergonadotropic amenorrhea. Whereas the POF rate was <50% in women below 30 years, it was 60% between 30 and 40 years. The cumulative dosage of cyclophosphamide also strongly influenced POF rate.
CONCLUSIONS: Our present results, with a high POF rate in Cyclophosphamide treated SLE patients demonstrate the urgent need for ovarian protection in this patient group. Besides POF these women are at high risk for premature atherosclerosis which is the major cause of death in lupus. Following preliminary encouraging experience in women with lymphoma, in whom the temporary induction of a prepubertal hormonal milieu during chemotherapy, has significantly decreased the risk of POF, we have initiated the PREGO-Study, comparing randomised monthly injection versus no injection of gonadotropin-releasing hormone analogue (GnRH-a) to young SLE patients during cyclophosphamide therapy. Department of Internal Medicine III and Institute for Clinical Rheumatology and Immunology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
BACKGROUND: With dramatically improved survival rates of SLE patients, comorbidity and long-term damage such as premature ovarian failure (POF) gain increasing importance. In the Erlangen cohort, 14% of cyclophosphamide treated patients younger than 41 years have POF, which is a common consequence of cyclophosphamide treatment.
PATIENTS AND METHODS: We tested the concentrations of FSH and LH, before, during and after cyclophosphamide treatment in 63 premenopausal women with SLE without ovarian protection and initiated the PREGO-Study (Prospective randomized study on protection against gonadal toxicity) in patients with SLE.
RESULTS: In lupus patients treated with cyclophosphamide, 60% suffered from POF and hypergonadotropic amenorrhea. Whereas the POF rate was <50% in women below 30 years, it was 60% between 30 and 40 years. The cumulative dosage of cyclophosphamide also strongly influenced POF rate.
CONCLUSIONS: Our present results, with a high POF rate in Cyclophosphamide treated SLE patients demonstrate the urgent need for ovarian protection in this patient group. Besides POF these women are at high risk for premature atherosclerosis which is the major cause of death in lupus. Following preliminary encouraging experience in women with lymphoma, in whom the temporary induction of a prepubertal hormonal milieu during chemotherapy, has significantly decreased the risk of POF, we have initiated the PREGO-Study, comparing randomised monthly injection versus no injection of gonadotropin-releasing hormone analogue (GnRH-a) to young SLE patients during cyclophosphamide therapy.

Manger K, Wildt L, Kalden JR, Manger B. Prevention of gonadal toxicity and preservation of gonadal function and fertility in young women with systemic lupus erythematosus treated by cyclophosphamide: the PREGO-Study.

5. Ovarian cryopreservation: a review

The review covers current options for ovarian tissue cryopreservation and transplantation and provides a systematic review of the existing literature from the last 10 years, taking into account all previously published reviews on the subject. The different cryopreservation options available for fertility preservation in cancer patients are embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. The choice depends on various parameters: the type and timing of chemotherapy, the type of cancer, the patient's age and the partner status. The different options and their results are discussed, as well as their putative indications and efficacy. The review concludes that advances in reproductive technology have made fertility preservation techniques a real possibility for patients whose gonadal function is threatened by premature menopause, or by treatments such as radiotherapy, chemotherapy or surgical castration.

Donnez J, Martinez-Madrid B, Jadoul P, Van Langendonckt A, Demylle D, Dolmans MM. Ovarian cryopreservation: a review Hum Reprod Update. 2006 Sep-Oct;12(5):519-35. Epub 2006 Jul 18.

Gerhard Leyendecker