Monika Bals-Pratsch

Transdermal testosterone substitution therapy for male hypogonadism.

A transdermal therapeutic system (TTS) for administration of testosterone was tested in healthy and hypogonadal men. To ensure adequate absorption, a testosterone-loaded film was applied to the scrotal skin. The TTS was designed to last for 22 h; over this time serum testosterone levels in normal men were moderately increased, with concentration curves almost parallel to basal levels. Seven hypogonadal patients also responded to TTS testosterone; serum testosterone levels were in the normal range during a 12-week treatment period. There were no side-effects. TTS testosterone offers a new approach to androgen substitution therapy.

Use of frozen-thawed testicular sperm for intracytoplasmic sperm injection

OBJECTIVE To determine the feasibility of using frozen-thawed testicular spermatozoa for intracytoplasmic sperm injection. DESIGN Prospective clinical study. SETTING A university hospital. PATIENT(S) One hundred seventy-five azoospermic men participating in a routine intracytoplasmic sperm injection program. INTERVENTION(S) The men underwent testicular biopsy for cryopreservation of tissue to be used in consecutive intracytoplasmic sperm injection treatment cycles. Their female partners underwent controlled ovarian hyperstimulation for conventional IVF treatment. MAIN OUTCOME MEASURE(S) Fertilization and pregnancy rates. RESULT(S) In 77% of the patients, spermatozoa could be harvested from the testis by an open testicular biopsy technique and used for intracytoplasmic sperm injection after freezing and thawing of testicular tissue. Histopathologic evaluation revealed a Sertoli cell-only pattern in 21%, maturation arrest in 60%, and hypospermatogenesis in 19% of the patients. In 2. 9% of the patients, carcinoma in situ or a germ cell tumor was detected. In all patients, viable spermatozoa could be visualized after the tissue samples were thawed. One hundred thirty-five intracytoplasmic sperm injection treatment cycles were performed, with a fertilization rate of 45% and a clinical pregnancy rate of 30% per oocyte retrieved. CONCLUSION(S) The use of frozen-thawed testicular tissue allows ovarian stimulation of the female partner to be timed and avoids cancellation of ovum pick-up when spermatozoa cannot be retrieved.

Experience with transvaginal ultrasound-guided aspiration of supernumerary follicles for the prevention of multiple pregnancies after ovulation induction and intrauterine insemination * †

OBJECTIVE To avoid multiple pregnancies caused by ovulation induction. SETTING Infertile couples treated in the Womens Hospital and the Institute of Reproductive Medicine of the University of Münster, Münster, Germany. DESIGN The outcome of ovulation induction in patients in whom supernumerary ovarian follicles were aspirated transvaginally was compared with the outcome in patients in whom this intervention was not necessary. In a second randomized prospective study, the efficacy of a low dosage of gonadotropins was compared with a higher dosage. PATIENTS Two hundred twenty-seven couples suffering from male infertility, unexplained infertility, incipient ovarian failure, and polycystic ovaries. INTERVENTIONS Aspirations were performed if more than three follicles were sized > 14 mm. MAIN OUTCOME MEASURE Number of (multiple) pregnancies. RESULTS During 232 ovulation inductions, 127 aspirations of supernumerary follicles were performed (54.7%). The pregnancy rate (PR) in these cycles was similar to cycles in which aspirations were unnecessary (24.4% versus 21.9%). The efficacy of 75 units of FSH administered daily during the recruitment phase of follicular development was equivalent to 150 units of FSH (PR: 32.4% versus 31.6%), but supernumerary follicles were fewer (26.5% versus 76.3%). Six twins, two triplets (multiple PR: 10.4%), and no ovarian hyperstimulation syndrome occurred. CONCLUSIONS Transvaginal aspiration of supernumerary follicles does not reduce the PR in ovulation induction. Supernumerary follicles can be avoided by low-dose administration of gonadotropins without compromising the PR.

PULSATILE GnRH‐THERAPY IN OLIGOZOOSPERMIC MEN DOES NOT IMPROVE SEMINAL PARAMETERS DESPITE DECREASED FSH LEVELS

In order to evaluate GnRH administration for the treatment of infertile men with elevated serum FSH levels we administered GnRH in pulses via portable electronic infusion pumps initially to seven patients with low sperm counts and high FSH values over 12 weeks and later to nine further patients over 24 weeks who also underwent testicular biopsies. Fifty microlitres containing 5 pg GnRH were infused subcutaneously for 1 min every 120 min in the short‐term study and every 90 min in the long‐term study. Although FSH levels could be lowered in both groups of patients, none showed any improvement in sperm count or other seminal parameters. Therefore, pulsatile GnRH treatment cannot be recommended for therapy of severe oligozoospermia with elevated FSH levels.

Schilddrüsenfunktionsstörungen und Sterilität der Frau

Bei Sterilitats-Patientinnen mit sublinischer Hypothyreose soll die Substitution mit Schilddrusenhormonen die Konzeptionsrate erhohen (1). In unserer Studie sollte der Zusammenhang zwischen Schilddrusen-Funktionsstorungen und Fertilitat untersucht werden, wobei zusatzlich morphologische Veranderungen der Schilddruse einbezogen wurden.

Predictive parameters for ovarian response to hyperstimulation with exogenous gonadotropins after suppression of gonadotropin secretion of the pituitary using a long-acting GnRH agonist

Individually adapted gonadotropin dosage is more successful than standardized schemes for ovarian stimulation prior to in vitro fertilization and embryo transfer. Unfortunately, differences in ovarian response can not be predicted reliably. In order to develop predictive parameters for ovarian response the data from 99 cycles in 69 patients were analysed retrospectively. Before initiating ovarian stimulation for in vitro fertilization, an untreated menstrual cycle was examined using a commonly used endocrinological screening protocol. The ovaries were then stimulated with exogenous gonadotropins after previous suppression of endogenous gonadotropin secretion using a long-acting GnRH-analogue. The predictive value of this endocrinological screening protocol for ovarian response was evaluated. Ovarian response was defined as the logarithmically transformed ratio of the serum estradiol concentration at ovulation induction, divided by the number of ampoules of exogenous gonadotropins administered. Comparison of the various hormone characteristics with ovarian response led to identification of two distinct groups of patients showing reduced ovarian response: those with elevated serum levels of FSH on the third cycle day (> 9 units/l, P < 0.0001), and those with elevated serum levels of estradiol on the third cycle day (> 190 pmol/l, P < 0.02). Patients with high serum levels of TSH in the TRH test responded poorly to ovarian stimulation (P < 0.05), but also showed significantly higher serum concentrations of FSH (P < 0.01). No parameter correlated positively with ovarian response.

Outcome of ICSI cycles using frozen–thawed surgically obtained spermatozoa in poor responders to ovarian stimulation: cancellation or proceeding to ICSI?

OBJECTIVE To investigate the ICSI outcome of the patients who produced four follicles or less after ovarian stimulation using frozen-thawed surgically obtained spermatozoa. STUDY DESIGN The patient cohort of this study was composed of a carefully selected group of 20 men suffering from obstructive and non-obstructive azoospermia and in whom spermatozoa had been seen in their harvested epididymal aspirates and testicular tissues and the cryopreserved specimens had been used for subsequent ICSI cycles. This group of men represent those in whom the female partners produced only four follicles or less after ovarian stimulation. RESULTS For the cases of obstructive azoospermia with MESA (n=6) a total of nine cycles was carried out. Four couples went through one cycle, one couple underwent two cycles, one couple accomplished three cycles. Out of the nine cycles, seven went to embryo transfer. No pregnancy occurred in the MESA-ICSI group of patients. The mean+/-S.D. number of oocytes per cycle was 2.556+/-1.236, the mean+/-S.D. number of embryos per transfer was 1.444+/-1.014. Two couples did not have an embryo replacement because of absence of fertilisation. The mean+/-S. D. number of gonadotropin ampoules was 53.88+/-37.30 and the mean+/-S.D. duration of ovarian stimulation was 13.38+/-4.534 days. For the cases of non-obstructive azoospermia with TESE (n=14) a total of 16 cycles was carried out. Thirteen couples went through one cycle, one couple accomplished three cycles. Out of the 16 cycles, 11 cycles went to embryo transfer. One pregnancy occurred in the TESE-ICSI group of patients, which produced live offspring. The mean+/-S.D. number of oocytes per cycle was 3.00+/-1.211, the mean+/-S.D. number of embryos per transfer was 1.313+/-1.195. Five couples did not have an embryo replacement, four of them because of absence of fertilisation and one because of abnormal fertilisation (3 PN). The mean+/-S.D. number of gonadotropin ampoules was 81. 77+/-53.40 and the mean+/-S.D. duration of ovarian stimulation was 16.71+/-3.667 days. CONCLUSION In our opinion, these data show that it is possible to achieve satisfactory fertilisation rates using frozen-thawed epididymal and testicular spermatozoa obtained from men with obstructive or non-obstructive azoospermia, but the limiting factor in reaching the stage of embryo transfer is the poor ovarian response to stimulation induction. It therefore seems preferable to cancel these cycles, in the hope that a better response might be obtained in a subsequent cycle, avoiding in this way financial and emotional implications.

Genetik der männlichen Infertilität

ZusammenfassungMännlicher Infertilität liegen in etwa einem Drittel der Fälle genetische Alterationen zugrunde. Dieser Tatsache sollte durch eine konsequente Diagnostik und umfassende Beratung des Kinderwunschpaares hinsichtlich möglicher Risiken vor Einsatz der modernen Techniken der assistierten Reproduktion Rechnung getragen werden.AbstractMajor principles of genetic failures, chromosomal alterations and the most common syndroms associated with male infertility should be taken into account before medical therapy and sophisticated techniques of assisted fertilization are applied to help a couple conceive. This review addresses the most common genetic reasons of male infertility with special regard to the importance for the clinical work up in daily routine and the potential risks for conceptus.