Poor Reproductive History Research Articles

Microdeletions in the Y chromosome and recurrent reproductive loss.

Objective: Investigators have recently linked sperm chromosomal aneuploidy frequency with recurrent miscarriage. A male genetic factor, based on such gross cytogenetic analysis, may imply a need for further investigation on the molecular level. Therefore, a pilot study was undertaken to assess whether a causal link between male gamete genetic abnormalities at the microscopic level and recurrent pregnancy loss could be established.Design: Seven male partners of women with recurrent pregnancy loss were tested for microdeletions in their Y chromosome.Materials/Methods: “Recurrent pregnancy loss” was defined as history of two or more spontaneous abortions. Male gamete genetic abnormalities at the microscopic level were tested in the Y chromosome, flanking the AZF region (“MYC” Test). Patient DNA was extracted via the buccal swab method, and PCR analysis was then performed on eighteen (18) loci (Promega Corporation, Madison, WI). Such a “MYC” Test result was considered positive when at least one such microdeletion in the Y chromosome was identified.Results: Five of the seven patients (71.4%) tested MYC positive. Two patients were teratozoospermic (strict sperm morphology < or = 4% normal). Three patients (60%) were normozoospermic. Of the three MYC positive patients: Their microdeletions ranged in number from 1 to 8. Their microdeletions were all found in the AZFd region, specifically at locus DYS236.Conclusions: Male genetic abnormalities, in the form of microdeletions in the Y chromosome, were found in the partners of women experiencing recurrent reproductive loss. Since this genetically abnormal semen was analyzed and tested as normal, semen analysis alone may prove insufficient for the exclusion of male factor etiology. Consequently, such “MYC” testing may be necessary to accomplish a thorough work-up for poor reproductive history cases. Undoubtedly, greater numbers of such cases should be similarly evaluated to confirm these early findings. Male genetic abnormalities may then prove, in certain cases, the causal factors for recurrent reproductive loss. Objective: Investigators have recently linked sperm chromosomal aneuploidy frequency with recurrent miscarriage. A male genetic factor, based on such gross cytogenetic analysis, may imply a need for further investigation on the molecular level. Therefore, a pilot study was undertaken to assess whether a causal link between male gamete genetic abnormalities at the microscopic level and recurrent pregnancy loss could be established. Design: Seven male partners of women with recurrent pregnancy loss were tested for microdeletions in their Y chromosome. Materials/Methods: “Recurrent pregnancy loss” was defined as history of two or more spontaneous abortions. Male gamete genetic abnormalities at the microscopic level were tested in the Y chromosome, flanking the AZF region (“MYC” Test). Patient DNA was extracted via the buccal swab method, and PCR analysis was then performed on eighteen (18) loci (Promega Corporation, Madison, WI). Such a “MYC” Test result was considered positive when at least one such microdeletion in the Y chromosome was identified. Results: Five of the seven patients (71.4%) tested MYC positive. Two patients were teratozoospermic (strict sperm morphology < or = 4% normal). Three patients (60%) were normozoospermic. Of the three MYC positive patients: Their microdeletions ranged in number from 1 to 8. Their microdeletions were all found in the AZFd region, specifically at locus DYS236. Conclusions: Male genetic abnormalities, in the form of microdeletions in the Y chromosome, were found in the partners of women experiencing recurrent reproductive loss. Since this genetically abnormal semen was analyzed and tested as normal, semen analysis alone may prove insufficient for the exclusion of male factor etiology. Consequently, such “MYC” testing may be necessary to accomplish a thorough work-up for poor reproductive history cases. Undoubtedly, greater numbers of such cases should be similarly evaluated to confirm these early findings. Male genetic abnormalities may then prove, in certain cases, the causal factors for recurrent reproductive loss.

Rat embryo culture to detect nutritional deficiency in women with poor reproductive histories

The cause of habitual early pregnancy loss is not known for most affected couples. It has been proposed that a deficiency of amino acids or other nutrients may contribute to early embryo loss, and an assay based on culture of rat embryos in human serum has been proposed to evaluate women with poor reproductive histories. We tested this assay in women with unexplained infertility ( n = 27), habitual abortion ( n = 15), and normal midtrimester pregnancies ( n = 10) by examining the ability of subject's serum to support the normal development of rat embryos in culture with and without supplemental vitamins and amino acids. Nonpregnant women with nutrient deficiencies identified in this manner were given oral supplements or placebo and were retested. A similar proportion of women in each group had serum that was unable to support the normal development of rat embryos without supplemental vitamins and amino acids. When oral supplements were used, most sera were able to support normal embryo growth. There were no seroconversions on placebo. In spite of the apparent success in producing seroconversions on oral supplementation, only two women conceived, one on the placebo treatment and one on nutritional supplements. Because serum nutrient deficiencies identified by rat embryo culture could not distinguish normal pregnant women from women with unexplained infertility or habitual abortion, and because of the low pregnancy rates, we could not confirm the utility of this assay for the general population of women with habitual abortion. If subtle nutritional deficiencies play a role in early pregnancy loss, it may require a more homogeneous population of women with, for example, a history of five or more spontaneous pregnancy losses.

Transvaginal ultrasonically guided follicular aspiration of equine oocytes: Preliminary Results

Equine embryo transfer has become commonplace in the past decade. One of the major reasons for embryo transfer in horses is as a treatment for infertile mares. Unfortunately, embryo recovery rate by conventional uterine lavage 7 days postovulation is extremely low in the older mare. The ability to collect oocytes directly from the follicle of the live mare would allow in vitro fertilization to be used as a technique for obtaining foals from older mares with poor reproductive histories. Several investigators have reported on collection of oocytes from slaughterhouse ovaries with subsequent maturation 9'11 and fe~ilization of these oocytes.2.s.1 z To date, only one foal has been produced by in vitro fertilization in horses. 9 Progress in in vitro fertilization is dependent upon a readily available supply of equine oocytes. Unfortunately, collection of oocytes at time of slaughter is an irreversible process. Several investigators have reported collection of equine oocytes via a standing flank laparotomy. 4,7,1° Recently, however, techniques have been developed for collection of oocytes from humans 3 and cattle e using a transvaginal ultrasonically guided follicular aspiration technique. This technique allows repeated collection of cocytes from both women and cows. Apparently, only one brief report on transvaginal collection of equine oocytes using ultrasonography has been reperted? The purpose of this study was to develop techniques for routine collection of equine oocytes using transvaginal ultrasonically guided follicular aspiration.

Sires influence fetal death in pigtailed macaques (Macaca nemestrina).

Computerized colony records were used to identify dams and sires whose reproductive histories while breeding in harem groups indicated high or low risk for producing fetal deaths. The monkeys were then singly caged and bred within and between risk conditions during 24- to 72-hour matings. Although the low- and high-risk sires did not differ in ability to achieve conceptions, the results revealed that reproductive history predicted subsequent fetal death rates, and sires made a substantial contribution. Overall, high-risk sires had a 4.86 times higher relative risk of producing fetal death than low-risk sires. Compared with this figure, high-risk dams had only a 2.64 times higher risk for fetal death than low-risk dams. The male effect was most evident in comparisons of between- and within-risk matings. Females with excellent reproductive histories experienced a threefold increase in fetal deaths when mated with high-risk males, whereas females with poor reproductive histories experienced almost a 50% reduction in fetal deaths when mated with low-risk males. The results show that male factors beyond fertility need to be considered when examining the causes of reproductive failure in captive primates.

Laminin immunized monkeys develop sera toxic to cultured rat embryos and fail to reproduce.

In a previous study antilaminin antibodies in a monkey with a poor reproductive history were found to be the cause of serum toxicity to cultured rat embryos. In the present study four monkeys were immunized with murine tumor laminin and a fifth with bovine serum albumin. Subsequently, sera from only the laminin immunized monkeys became toxic to cultured rat embryos. This serum toxicity was not mediated by complement but did require the antibody to have a divalent structure. Finally, mating trials were conducted with two of the laminin immunized monkeys that previously had excellent reproductive histories. Based on progesterone levels and observation the monkeys continued to have normal menstrual cycles but failed to initiate a successful pregnancy following immunization in over 2 years of mating trials. These data demonstrated that antibodies against laminin could have prevented conception or could have interrupted pregnancy because of embryotoxicity or failure of implantation.

Long term follow-up of women with hypertension in pregnancy

The reproductive history and the present health status of 66 patients who had had a pregnancy complicated by hypertension during the period 1972–1982 were retrospectively studied. Hypertension in pregnancy is a poor prognostic factor not only for the future development of hypertension but, also, as it is associated to a very poor reproductive history. Such complications are more frequent in pregnant women with very high blood pressure ( 160 100 ). In fact, in the case of a previous pregnancy, this group of patients had experienced a high rate of abortions (31.7%), premature deliveries (17.8%) and perinatal mortality (21.4%). Moreover, these women are subject to a higher risk (56.5%) of developing hypertension in successive pregnancies. Risk factors for determining the future development of hypertension are: familiar hypertension, the severity of hypertension during pregnancy and pluriparity.

Electrocoagulative removal of endometrial cysts in the mare

Six mares had endometrial cysts removed by endoscopic electrocoagulative surgery. These mares exhibited poor reproductive histories and endometrial cysts were the only detectable abnormalities. In each case, at least two cysts greater than 2.5cm were present. One mare subsequently produced a live foal; two are presently in foal; one conceived but absorbed; one formed more cysts after surgery; and one has not yet been bred. Histologically, the walls of the cysts contained entire lamina propria, relatively normal endometrial glands, and small cystic spaces.

A study of institutionalized mentally retarded patients in Manitoba: over-representation by Canadian Indian children.

During analysis of data on 406 severely and profoundly mentally retarded children and their families in Manitoba a marked excess of Canadian Indian children was observed. There was no evidence to suggest that the over-representation by native children was due to an increased propensity of Indian families to institutionalize their children nor were these patients more profoundly retarded or more physically handicapped than the non-Indian children studied. Further analysis showed that Indian children were primarily over-represented in the groups with acquired retardation, autosomal recessive genetic disorders, idiopathic retardation with seizures and idiopathic retardation with malformations or dysmorphic signs. Review of other demographic findings indicated that other factors potentially predisposing to retardation, including low socioeconomic status, illegitimacy, high birth order, poor maternal reproductive history and increased consanguinity, were more common in the histories of native children. Severe and profound mental retardation has been said to occur equally in all strata of society. This evidently was not so in this Canadian population and the Indian child may be at special risk. Health care workers should be aware of possible predisposing factors for retardation in this group if reduction of the incidence of this major problem is to be achieved.

Equine pregnancy examination using diagnostic ultrasound

Six mares had endometrial cysts removed by endoscopic electrocoagulative surgery. These mares exhibited poor reproductive histories and endometrial cysts were the only detectable abnormalities. In each case, at least two cysts greater than 2.5cm were present. One mare subsequently produced a live foal; two are presently in foal; one conceived but absorbed; one formed more cysts after surgery; and one has not yet been bred. Histologically, the walls of the cysts contained entire lamina propria, relatively normal endometrial glands, and small cystic spaces.

Pregnancy outcomes following Tompkins metroplasty

Eighteen patients with poor reproductive histories and 2 patients with primary infertility underwent Tompkins metroplasty for a septate uterus. There were 19 pregnancies within 2 years of surgery, and 11 patients had at least 1 viable pregnancy, for an overall success rate of 55%. One of the infertile patients conceived and delivered. The average fecundability rate for the first 24 months was 0.078 (normal, 0.20). The cumulative pregnancy rate at 27 months was 94% by the life-table method. The group of patients (n = 14) with two or more losses and no other major risk factors for reproductive failure had higher fecundability and a better success rate (71%). The Tompkins metroplasty is a technically simple procedure with a success rate similar to that of the Jones procedure.

Familial mutagen sensitivities: are these the hallmarks of meiotic or mutator mutants in humans?

Mutagen hypersensitivity (MHS) has been found to be associated with abnormalities in DNA metabolic processes in many prokaryotic and eukaryotic organisms. The study of fibroblasts derived from humans with genetic diseases believed to have altered DNA metabolism, has also revealed patterns of MHS. In this paper results are presented that suggest MHS patterns unrelated to obvious disease can be inherited in a dominant fashion. As these individuals exhibiting MHS patterns have been observed in families with poor reproductive history, new syndromes, or ontogenetic problems (including malignancies) there may be a causal relationship between these events and the MHS. These events which may have a genetic basis appear as maternal or paternal effect mutants as the consequences are observed in reduced reproductive fitness or abnormal progeny. Since these effects are similar to the events precipitated by the meiotic or mutator mutants in Drosophila, it is speculated that the MHS patterns may be the hallmarks of such mutants in man.

Thyroid function in human pregnancy: IX. Development or retardation of 7-year-old progeny of hypothyroxinemic women

Progeny of women, whose thyroid function was studied gestationally, had psychological and/or neurologic examinations at 8 months, 4 years and 7 years of age. In more than 100 pregnancies (at least 3 per cent of total pregnancies) hypothyroxinemia occurred and was treated adequately or inadequately. Children were delivered after uncomplicated pregnancies (except hypothyroxinemia), had birth weights of at least 2,500 grams, and were excluded when postnatal insults intervened. At 8 months and 4 years progeny of inadequately treated hypothyroxinemic women had the lowest psychological scores. Now 246 7-year-old children have been examined psychologically and neurologically (earlier data on only 101). Definite trends and a few statistically lower psychological scores of progeny of inadequately treated hypothyroxinemic pregnant women are compared with better psychological scores of 7-year-old children born to euthyroid and adequately treated hypothyroxinemic women. In six sibling sets outcome was better when hypothyroxinemic women were treated with adequate thyroid replacement therapy. If a woman has a poor reproductive history, early in a subsequent gestation, thyroid status should be examined and adequate thyroid medication considered seriously.

Listeria monocytogenes septicemia in pregnancy.

A case of Listeria monocyto-enes septicemia in a patient with a poor reproductive history is presented. The clinical aspects and implications of this infectious disease during pregnancy are discussed, and the role of Listeria as a cause of recurrent pregnancy wastage is summarized.

THE EFFECT OF SINGLE PRENATAL AND NATAL COMPLICATIONS UPON THE DEVELOPMENT OF CHILDREN OF MATURE BIRTHWEIGHT

Children of mature birthweight were followed prospectively to the end of their first year in school to determine the effect upon their development of complications in one of the following areas: pregnancy, labor, or obstetrical anesthesia. Non-English speaking and one-parent families, and children of mothers with poor reproductive histories or infections during pregnancy were excluded. Only in the comparison of the children exposed to preeclamptic toxemia with their controls was it possible to demonstrate an unfavorable difference in intelligence and behavior. The difference was small and barely significant statistically.

SPERM-AGGLUTINATING ANTIBODIES AND DECREASED FERTILITY IN PROSTITUTES

Forty-eight prostitutes were studied for the presence of sperm-agglutinating antibodies. Thirty-five, or 72.7%, were positive. A control group of 25 unmarried women had a 20% incidence of reactions. The specificity of the microagglutination test is discussed. No false positive reactions have occurred from pH, dilution effects, or washing technics used in our procedure. The test reaction is related to seminal plasma-coating antigen. Prostitutes have a poor reproductive history and a high incidence of abortion. Our data suggest a relationship between circulating antibody titers and decreased fertility, but no relationship to increased abortion rate. Tissue-fixed antibodies are demonstrated in cervical and endometrial tissue of 5 prostitutes with circulating antibody titer. The significance of this finding is discussed.

Some Abnormalities of the Bovine Endometrium

Two types of glandular abnormality and nodules of lymphoid tissue in the bovine endometrium have been described. These abnormalities appeared more frequently in the endometrium of cattle with a poor reproductive history than in apparently normal cattle. In two separate populations of cows from widely separate locations, however, this relationship was only evident in one of the groups and not in the other. In view of this observation, the suggestion that these abnormalities may be associated with poor reproductive performance must be taken with reservations. A search for these and possibly other types of abnormalities and a determination of their relationship to reproductive performance on a wider scale than has been done to date could possibly add useful information to our knowledge of abnormal reproductive performance.