Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing hormone, melatonin and cortisol in infertile women with subclinical hypothyroidism

Preliminary data have suggested that female infertility due to corpus luteum insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin- releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been recommended to achieve pregnancies in subclinical hypothyroid women. This controlled study was carried out in order to investigate the biochemical diagnosis of subclinical hypothyroidism as a possible infertility factor. Five infertile patients (aged 25-36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years) with normal thyroid function (stimulated TSH <15 microU/ml), regular cycles and no history of infertility were studied in the early follicular phase. In the pre-study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle function of patients and controls was compared by the method of LH pulse pattern analysis. Therefore blood samples were drawn every 10 min during a 24 h period. Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end of the 24 h blood sampling period confirmed the difference in stimulated TSH values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin showed no differences between patients and controls for pulse frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean. Even the hypothyroid patient had a normal LH pulse pattern. Additional measurement of melatonin in pooled sera every 30 min gave the well-documented diurnal profiles during day and night for both groups. Patients had significantly higher melatonin values at seven time points during the night. Peaks for LH, TSH, prolactin and cortisol were correlated with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in female infertility cannot be explained by subclinical hypothyroidism and thus should not be treated with L-thyroxine for fertility reasons.      

Clinical and endocrine follow-up of patients after testicular sperm extraction

OBJECTIVE: To evaluate the risk of testicular damage from testicular biopsies that are carried out for testicular sperm extraction (TESE) in infertile men. DESIGN: Prospective controlled clinical study. SETTING: Academic hospital. PATIENT(S): Forty infertile males with azoospermia.Examination of the clinical, endocrine, biochemical, and sonographic data in average after 18 months after TESE was performed. MAIN OUTCOME MEASURE(S): Measurements before and after TESE: hormone values, testicular size, morphologic characteristics, and power Doppler after scrotal sonography. RESULT(S): Comparison of preoperative and postoperative values of basal testosterone, FSH, LH, and estradiol levels did not reveal any differences. Twelve of 26 patients had subnormal testosterone values before TESE; 14 of 39 patients had subnormal levels afterward. Postoperative sonographic measurements showed no significant difference of the testicular volume as compared with the preoperative values. Results of power Doppler sonography revealed pathological conditions (n = 5) in patients with former iliacal or testicular operations. CONCLUSION(S): Endocrine testicular function and testicular size were not impaired after testicular biopsy when compared with preoperative data. However, patients with nonobstructive azoospermia seem to be at risk for androgen deficiency due to primary testicular failure after repeated testicular biopsies.     

Genetik der männlichen Infertilität

Major 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.     

Pro und Kontra transdermaler Systeme

The estrogen concentrations obtained with transdermal therapeutic systems (TTS) are closer to the premenopausal methods than those yielded by any other method currently available. Constant estradiol concentrations are achieved, comparable with those seen earlier in the follicular phase. When hormone replacement therapy is given by mouth, the dosage of estradiol needed to reach effective active ingredient levels is 40 times that used for TTS treatment, and then the levels fluctuate markedly with supraphysiological peaks and subnormal nadirs. The high doses are needed for oral administration because estrogen is very strongly metabolized during passage through the liver. The liver is “flooded,” especially with oestrone, estriol, 16α-hydroxyestrone and the catechol estrogens. Increased synthesis of hepatic proteins such as angiotensinogen or thyroxine-binding globulin (TBG) and various coagulation factors arises, and hyperlipoproteinemia can occur. With transdermal estrogen replacement, the oestradiol passes directly into the systemic circulation and thus to the target organs. In the presence of liver disease, gastrointestinal disease, venous thromboembolism, and thyroid disease, transdermal estrogen replacement therapy is therefore indicated in preference to the corresponding oral therapy. If the indications are strictly observed, estrogen treatment by the transdermal route can be justified even after cardiac infarction.     

A novel homozygous disruptive mutation in the SRD5A2-gene in a partially virilized patient with 5alpha-reductase deficiency

Steroid 5alpha-reductase deficiency is a rare autosomal recessive disorder caused by mutations in the SRD5A2-gene, resulting in diminished dihydrotestosterone (DHT) formation and, hence, in a severe virilization deficit of the external genitalia in patients with 46,XY karyotype. The phenotype of affected individuals is variable and has been reported to range from completely female over genital ambiguity to normal male, depending on the type of mutation and its effect on enzyme activity. Here we report an adolescent 46,XY patient with predominantly female appearance, who had been gonadectomized in early infancy. Genital status revealed a urogenital sinus equivalent to Prader stage III. Molecular genetic analysis demonstrated a homozygous point mutation in exon 2 of the SRD5A2-gene, leading to a premature termination in codon position 111 of the 5alpha-reductase 2 enzyme, and not allowing formation of a functional 5alpha-reductase type 2 enzyme. This case demonstrates that even despite a complete loss of function of 5alpha-reductase type 2, marked virilization is possible, most likely the result of a testosterone (T) effect during foetal life.     

Andrologische Diagnostik und Therapie

Ohne Zusammenfassung     

Androgen receptor disorder in three brothers with bifid prepenile scrotum and hypospadias

Three brothers with congenital transposition of the penis, scrotal hypospadias, bifid scrotum, and bilateral undescended testes are described. Further signs of incomplete virilization, but no gynecomastia were seen. LH and FSH were elevated, whereas testosterone levels were reduced or in the normal range. Serum concentrations of 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, 5 alpha-dihydrotestosterone and estradiol measured in two affected brothers were in the normal range. Fibroblasts from scrotal skin biopsies performed in two patients showed normal 5 alpha-reductase activity (419 and 214 pmol.(mg protein)-1.h-1; normal greater than 1), whereas androgen receptors had reduced maximal binding capacity (Bmax 4 and 14 fmol.(mg protein)-1; normal greater than 18) and an increased equilibrium dissociation constant (0.7 and 1.26 nmol/l: normal 0.2 +/- 0.08) indicating a quantitative and qualitative androgen receptor defect. These patients represent a further variant of androgen insensitivity.     

Pregnancies achieved after frozen-thawed pronuclear oocytes obtained by intracytoplasmic sperm injection with spermatozoa extracted from frozen-thawed testicular tissues from non-obstructive azoospermic men.

The use of frozen-thawed testicular tissue as a source of spermatozoa for intracytoplasmic sperm injection (ICSI) in non-obstructive azoospermia yields favourable fertilization and pregnancy rates while avoiding both repetitive biopsies and unexpected cycle cancellations. Spermatozoa were obtained from frozen-thawed testicular biopsy specimens from 67 non-obstructive azoospermic men. Following fertilization, supernumerary two pronuclear (2PN) oocytes were frozen. After thawing, 17 cycles of embryo transfer were carried out with a mean number of 2.7 embryos and a mean cumulative embryo score (CES) of 18.3 per transfer. The clinical pregnancy and implantation rates per transfer in these cycles (23.5 and 8.3% respectively) were comparable to those of fresh embryo transfers (35.7 and 12.7% respectively) with a mean number of 2.7 embryos and a mean CES of 28.7 per transfer. Abortion rates, although higher with cryopreserved 2PN oocytes were not significantly different. With this approach, cryopreservation of supernumerary 2PN oocytes can be used to improve the cumulative pregnancy rates in a severely defective spermatogenetic population. To our knowledge, these are the first pregnancies reported which have been obtained by the transfer of cryopreserved pronuclear oocytes obtained from ICSI using cryopreserved testicular spermatozoa.     

Wie h?ufig ist nach Knochenmarkstransplantation mit einer Einschr?nkung der m?nnlichen Fertilit?t zu rechnen?

Ohne Zusammenfassung