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Genetic approaches to unraveling reproductive disorders: examples of bedside to bench research in the genomic era.

Despite the rapid advances in medical genetics, many clinicians and investigators remain unaware of the general approaches that can be used to map genes. Although there are specific challenges to using genetic approaches in reproductive medicine, the following report summarizes mapping efforts for three diseases: adrenal hypoplasia congenita, hypergonadotropic ovarian failure, and polycystic ovary syndrome. The themes of rare and novel phenotypes, genetically homogenous populations, and genotype/phenotype correlations are emphasized.

DAX-1 Orphan Nuclear Receptor↗

In vitro suppression of murine blastocysts growth by sera from women with reproductive disorders.

Early mouse embryos at the two-cell stage were cultured in medium supplemented with sera from women with primary and secondary multiple spontaneous abortions and with long term unexplained infertility as compared to sera obtained from normal fertile women and pooled human male sera. On the basis of microscopic observation and uptake of 3H-thymidine we report a relationship between reproductive histories and the presence of a serum embryo inhibition factor in eight of ten sera samples from women with primary habitual abortions, six of ten sera from women with secondary habitual abortions, and ten of ten sera from women with unexplained infertility. This activity occurs independently of positive maternal antipaternal lymphocytotoxicity. Fractionation of serum samples by ammonium sulphate precipitation, resulted in removal of the embryo-inhibition factor with the IgG fraction in four of five primary habitual abortion cases and in two of five secondary habitual abortion patients, but not in the case of unexplained infertility. We propose that the appearance of such inhibition factor may be of relevance in the etiologies discussed in this paper and may possibly provide the basis for a new classification of idiopathic spontaneous habitual abortions, i.e. positive or negative for the embryo inhibition factor.

Abortion, Habitual↗

Reproductive disorders affecting fertility in endometriosis.

The classical concept of endometriosis as a cause of infertility is challenged. Traditionally, both surgical and medical therapy of endometriosis-associated infertility has focused on eliminating or reducing the visible implants. The classic 6-month medical approach has been a failure, and surgery may moderately enhance fertility, but its benefit in the absence of adhesions is still doubtful. Recent studies have shown that endometriosis is characterized by an aberrant response to sex steroid hormones, resulting in pleiotropic dysfunctions of the reproductive system involving the uterine, peritoneal and ovarian micro-environment. Studies on endometriosis and IVF have been highly relevant in revealing the pleiotropic dysfunctions in patients with endometriosis, although the results should be interpreted with caution. The conclusion seems to support the view that infertility in patients with endometriosis is primarily dysfunctional, rather than lesional, in origin. It is concluded that the place of medical therapy in endometriosis should be reviewed and that the surgical approach needs to be complemented by appropriate medical therapy to restore fertility.

Endometriosis↗

Isolation of Toxoplasma gondii from goats with history of reproductive disorders and the prevalence of Toxoplasma and chlamydial antibodies.

The prevalence of antibodies to Toxoplasma gondii and Chlamydia psittaci was assessed in goats with a history of abortion, stillbirth and neonatal mortality. Antibodies were detected in 540 (30%) and 57 (3.2%) goats out of 1799 tested by indirect haemagglutination and complement fixation tests, respectively. Toxoplasma gondii was isolated for the first time in Botswana from 22 out of 81 sets (27.2%) of foetal tissues, maternal and foetal cotyledons and uterine tissues of goats which had previously aborted or given birth to stillborn or weak kids that died within two days of birth. These results implicate T. gondii and C. psittaci, but especially the former, to be associated with caprine reproductive problems and require appropriate control measures.

Abortion, Veterinary↗

Estrogen-related mood disorders: reproductive life cycle factors.

Women are at higher risk throughout their reproductive lives than are men for major depression. Numerous molecular and clinical studies have implicated estrogen in modulating brain function including that related to mood. In an attempt to present a conceptual model, the literature of the past 30 years on mood and well-being throughout reproductive life is reviewed as it relates to activity of endogenous, bio-identical, and synthetic estrogen in women. Results indicate that sudden estrogen withdrawal, fluctuating estrogen, and sustained estrogen deficit are correlated with significant mood disturbance. Clinical recovery from depression postpartum, perimenopause, and postmenopause through restoration of stable/optimal levels of estrogen has been noted.

Contraceptives, Oral, Hormonal↗

[Risk of reproduction disorders in carriers of mutual chromosomal translocations, and methods for detection of translocation carriers].

It is believed that the method of detection of chromosomal translocation carrier state may be a prognostic factor for the risk of giving birth to an ill child with unbalanced karyotype. For verification of this view 30 families were studied which had balanced mutual translocations identified by means of GTG banding technique in the Genetics Laboratory of the Child's Health Centre. In each family the risk was estimated of the development of an undifferentiated karyotype in live born offspring and fetuses in the 2nd trimester of pregnancy using a method evolved by Stengel--Rutkowski et al. (1988). In the group of families identified by examination of a child with abnormalities the individual risk of development of an undifferentiated karyotype in a newborn was from 0.45% to 19.78% and in a fetus it was 4.5% to 46%. In the group of families identified by spontaneous abortion the risk in the newborns was from 0 to 7% and in the fetuses in 2nd trimester it was 0 to 35%, while in the families undergoing cytogenetic examinations for indications other than reproduction disturbances the risk of an unbalanced karyotype in the newborns was from 0 to 23%, and in the fetuses from 0 to 34%. Since in each group of families high-risk translocations were found, the used methods of preliminary estimation of the risk based on the used ways of family identification are open to reservations.

Chromosome Banding↗

[Management of reproduction disorders in spinal cord injured adolescents].

Adolescence is a period of research of sexual identity. How does a teenager build himself when a paraplegic or quadriplegic? How can the team of nursing staff help him? First we shall study the erection and the sexual relations and secondly we shall study the procreation issue. It is necessary to have early concrete information really suitable for a neurologic definition of a spinal cord injury and to conserve sperm before having complications of urinary infections. We inform 24 paraplegic or tetraplegic teenagers at the CMPA in Neufmoutiers and the CECOS at the Cochin Hospital in Paris.

Adolescent↗

[The prevention of reproductive disorders occurring during the chemotherapy of women of child-bearing age suffering from Hodgkin's disease].

A menstrual function was studied in 24 females treated by drugs for advanced stages of Hodgkin's disease. 17 of them received oral contraceptives for preventing gonadotoxic effect of cytostatic agents (the study group). 7 women did not use contraceptives (the control group). After chemotherapy menstrual cycle was normal in 88.2% of patients of the study group, whereas in 71.4% of controls artificial menopause developed. Oral contraceptives can be recommended to protect the ovaries in the course of chemotherapy.

Adolescent↗

Evaluation of serum-associated embryotoxicity in women with reproductive disorders.

PURPOSE: Our purpose was to determine whether some cases of infertility may be due to serological factors inhibiting development of the embryo. METHOD: We examined the effect of infertile women's sera on the expansion, attachment, and spreading of mouse blastocysts in culture. Cell marker expression was also assayed by an indirect immunofluorescence technique. Serum samples from 75 infertile women were compared to the effect of 24 control AB sera. RESULTS: After 72 hr, blastocyst spreading was significantly different depending on whether cultured in sera from women with unexplained infertility, anovulatory infertility, diethylstilbesterol exposure or controls. Neither sera from women with mechanical infertility (14) nor sera from women with endometriosis (8) affected blastocyst growth in culture. CONCLUSIONS: Inhibitory sera were capable of reducing cytokeratin expression but had no effect on placental alkaline phosphatase or concanavalin A expression by blastocyst cells. It can be inferred that the inhibitory effect of sera from women with certain types of infertility might be due to damage to the cytoskeleton. This in vitro assay may predict the success or failure of IVF.

Adult↗

A study of a herpesvirus isolated from dairy cattle with a history of reproductive disorders.

Three strains of herpesvirus were recovered from cows with vulvovaginitis. The three isolates (85/BH 16TV, 85/BH 17TV, 85/BH 18TV), when compared by cross serum neutralization (SN) tests, were found to be antigenically identical. They were serologically distinct from infectious bovine rhinotracheitis (IBR) virus and Bovid herpesvirus 2 (BHV2), while they cross reacted with bovine herpesvirus DN-599. Besides the serologic aspects, the three isolates appeared to share common biological, physical and morphological properties with the newly recognized bovine herpesviruses, of which DN-599 is a representative strain.

Animals↗

A cytogenetic study of Kuwaiti couples with infertility and reproductive disorders: short arm deletion of chromosome 21 is associated with male infertility.

Chromosomal anomalies may be a reason for both male and female infertility. The aim of this study was to investigate the contribution of chromosomal abnormalities in sterile couples from Kuwait. A total of 118 patients with clinical diagnosis of infertility was analyzed using cytogenetic banding techniques. Common chromosomal abnormalities were detected in 12 patients. We describe here one new case of an infertile male with the karyotype 46,XY, del(21)(pter;q11.2). The overall incidence of 11% abnormality indicates that routine chromosome analysis of infertile couples in Kuwait should be considered before the planning of intracytoplasmic sperm injection.

Adult↗