Increased risk of preterm delivery and pre-eclampsia in women with polycystic ovary syndrome and hyperandrogenaemia.

OBJECTIVE: To study the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome (PCOS), and to examine the role of hyperandrogenaemia. DESIGN: Cohort study. SETTING: Singleton pregnancies in women with PCOS identified at a private fertility clinic during 1997-2010 and a background population including all singleton deliveries at Hvidovre Hospital, Denmark, in 2005. POPULATION: A cohort of 459 women with PCOS and a background population of 5409 women. METHODS: Obstetric outcomes were extracted from national Danish registries and odds ratios (ORs) were calculated by multiple logistic regression analysis, adjusting for age, parity, and body mass index. MAIN OUTCOME MEASURES: Risk of pre-eclampsia, preterm delivery, and small for gestational age offspring in the entire PCOS population and in a subsample with hyperandrogenaemia. RESULTS: Women with PCOS had an increased risk of preterm delivery <37 weeks of gestation (OR 2.28; 95% confidence interval, 95% CI, 1.51-3.45; P < 0.0001). The elevated risk was confined to hyperandrogenic women with PCOS: preterm delivery before 37 weeks of gestation (OR 2.78; 95% CI 1.62-4.77; P < 0.0001), and was not seen in normoandrogenic women with PCOS (OR 1.35; 95% CI 0.54-3.39; P = 0.52). The overall risk of pre-eclampsia was not elevated (OR 1.69; 95% CI 0.99-2.88; P = 0.05) compared with the background population, but was significantly increased in the hyperandrogenic subsample (OR 2.41; 95% CI 1.26-4.58; P < 0.001). The risk of small for gestational age offspring was similar in all groups. CONCLUSION: Women with PCOS had an increased risk of preterm delivery compared with the background population. The increased risk was confined to hyperandrogenic women with PCOS who had a two-fold increased risk of preterm delivery and pre-eclampsia.

Feminizing effect of mesonephros on cultured differentiating mouse gonads and ducts.

Gonads were removed from fetal mice at about the time that gonadal sex differentiation occurs. The gonads were cultured in vitro with or without their mesonephric tissue. When gonads and ducts removed from sexually undifferentiated fetuses were cultured together, the gonads of both sexes developed female characteristics, whereas gonads cultured without mesonephros developed according to the sex of the fetus from which they were removed. Gonads of sexually differentiated fetuses developed whether they were cultured with or without the mesonephros.

Mapping of functions in the R-plasmid R388 by examination of deletion mutants generated in vitro.

Mutant plasmids in which large segments of R388 DNA are deleted were constructed in vitro from two R388::TnA (Tn801) plasmids, using the BamHI site of TnA and the BamHI and BglII sites of R388. These deletion mutants permitted mapping of genetic functions into the restriction map of R388.

Meiosis-inducing and meiosis-preventing substances in human male reproductive organs.

The initiation of meiosis is controlled by two substances, a meiosis-inducing substance (MIS) and a meiosis-preventing substance (MPS). These have been shown to be present in reproductive organs of both sexes of different mammals. In this investigation MIS and MPS were also shown to be present in man. MIS was found in fetal and adult epididymides and testes. MPS was obtained from the tests of one fetus, which was delivered by laparotomy. MPS could not be found in the testes of another fetus, which was aborted by prostaglandin F2 alpha and oxytocin. No or only weak MPS activity was detectable in the adult testis. This report indicates that continued spermatogenesis might be influenced by the MIS:MPS ratio. MPS was shown not to be species-specific. MIS and MPS activity have been evaluated by qualitative scoring of the different germ cell stages present in fetal gonads after culture in used media containing MIS or MPS.

Is low temperature of the follicular fluid prior to ovulation necessary for normal oocyte development?

Because low temperature in the testis is essential to normal spermatogenesis, we speculated whether a low follicular temperature could also be of importance for the oocytes as they resume meiosis at ovulation. We measured the temperature of the follicular fluid and of the ovarian stroma in 26 follicles in 14 women. In 25 follicles (13 women) the follicular fluid was colder than the ovarian stroma. This temperature difference increases toward ovulation (maximum, 2.3 degrees C). In one case, the measurements of the follicular/stromal temperature difference showed an inverse pattern, the follicular fluid being 0.2 degree C warmer than the stroma. This woman was infertile, and oocyte evaluation for in vitro fertilization had five times shown the oocytes unable to divide in culture. The present study supports the idea that low temperature of the follicular fluid prior to ovulation may be essential for normal oocyte development.

Abnormal growth of ovarian antral follicles in breast cancer patients.

Ovarian antral follicles from patients with breast cancer were compared with follicles from healthy women. Steroid levels in the follicular fluid and the health status of the follicles were evaluated. Follicles were judged to be healthy or atretic by flow cytometric determinations of the deoxyribonucleic acid content of aspirated granulosa cell nuclei. Fifteen of the 25 follicles (60%) from the cancer patients contained unmeasurable or abnormally low steriod levels (i.e., less than 100 ng/ml) which were significantly (P less than 0.001) lower than in follicles of the same health status from healthy women (500 to 1000 ng/ml). It is speculated whether substances other than the usual follicular steriods are produced by the cancer patients, which stimulate mitotic activity of the granulosa cells.

Prediction of ovulation.

The purpose of this investigation was to evaluate all available ovulatory diagnostics with respect to sensitivity, specificity, diagnostic specificity (predictive value of a positive test, PVP) and diagnostic sensitivity (predictive value of a negative test, PVN). Twenty-one ovulatory women with more than 3 years of infertility problems were included in the study. PVP and PVN were highest for detection of urinary luteinizing hormone (LH) peak at ovulation (PVP = 90%, PVN = 95%) and for serum-estradiol peak 1 day before ovulation (PVP = 83%, PVN = 97%). The predictive values were lower for all other tests. The PVP (54%) and PVN (90%) were rather low for detection of ovulation with vaginal electric impedance. However, all ovulations were predicted when urinary LH peak and vaginal impedance were combined. Two women were stimulated with human chorionic gonadotropin to investigate a possible connection between the LH peak and the preovulatory vaginal electric impedance. No close connection between them could be demonstrated. Basal body temperature should not be used for the prediction of ovulation (PVP = 25%). We suggest that ovulation should primarily be predicted from the identification of the urinary LH peak and that other methods be supplementary.

Is resumption of meiosis in the human preovulatory oocyte triggered by a meiosis-inducing substance (MIS) in the follicular fluid?

Aspirates from 31 ovarian follicles and 2 corpora lutea of 26 women at different stages of the menstrual cycle were investigated for activity of meiosis-inducing substance (MIS) and meiosis-preventing substance (MPS). The aspirated follicles were classified as dominant (i.e., preovulatory), healthy, or atretic according to their size, steroid hormone content, and stage of the menstrual cycle. To test for MIS and MPS activity, gonads of sexually undifferentiated fetal mice were cultured in media containing either 15% follicular fluid aspirate (test gonads) or 15% human blood serum (control gonads). MIS activity is present in follicular fluid if the test testes contain more meiotic germ cells than the control testes. MPS activity is present if the test ovaries have less meiotic germ cells than their controls. MIS activity was present only in healthy follicles of the late follicular phase (12 of 15 follicles). No MIS activity was seen in healthy or atretic follicles from other phases of the menstrual cycle. The MIS activity is apparently unrelated to the composition of steroids in the follicular fluid. MPS activity was not found in any of the follicles. It is proposed that the preovulatory resumption of meiosis may be triggered by a MIS in the follicular fluid.

Ultrastructure of germ cells and adjacent somatic cells correlated to initiation of meiosis in the fetal pig.

The ultrastructure of female and male germ cells and associated somatic cells were studied in morphologically sex differentiated fetal pig gonads from day 27 to day 95 post insemination. Before meiosis starts in the ovary, the organelles of germ cells and somatic cells of both sexes are poorly developed. In oocytes in leptotene stage, the endoplasmic reticulum attains close proximity to the plasma membrane forming characteristic contact areas which in addition are only seen in male germ cells of the same age. As meiosis progresses, the organelles of the oocyte increase in number and degree of differentiation. In particular the ER is prominent in the diplotene stage. At midgestation the male germ cells become polarized, the organelles gathering at one side of the nucleus. In the granulosa cells the number and extension of organelles increase concomitantly with the oocytes proceeding through meiosis. The Sertoli cells grow progressively complex in shape, with numerous mitochondria and a prominent ER, whereas the Golgi complex remains poorly developed. Small dense bodies are present both in germ cells and somatic cells. They are electron dense, membrane bounded, rounded or elongated granules often connected with endoplasmic reticulum. No activity of peroxidase, catalase or acid phosphatase could be traced in the granules, making them improbable candidates as peroxisomes or lysosomes. Their number is high in all germ cells and somatic cells on day 27 post insemination and in germ cells in leptotene stage.

Evolution of transposable elements.

Transposable elements are at an advantage compared with other DNA sequences. This has led to the generation of transposable systems from a variety of different sources. Once fabricated, these elements can very simply acquire accessory genes, such as those that encode resistance to antibiotics. This can lead to further evolutionary advantages and to their shorter-term importance. It is likely that many new transposable systems will be discovered, owing to the advantages conferred on sequences by transposition, and it is certain that many new transposons that encode varying drug resistance patterns will arise.

Influence of mesonephros on foetal and neonatal rabbit gonads. II. Sex-steroid release by the ovary in vitro.

To test whether the mesonephros influences the steroid hormone release by the foetal and neonatal ovary, rabbit ovaries were cultured with and without the mesonephros for a period of 5 days. The media were harvested once every day and analyzed by RIA for the content of testosterone, oestradiol and progesterone. Mesonephros produced progesterone only at day 20 pc. At day 21 and 28 pc significant amounts of all three hormones were produced. The media of the co-cultures of ovaries with the mesonephros contained on day 23 and 28 pc less testosterone. On day 23 pc less les and on day 3 pp more oestradiol was found in the media of the co-cultures. At day 21 pc progesterone release was increased by the mesonephros. It could be concluded that the mesonephros is able to synthetize steroids and possesses the capacity both to lower and to increase ovarian steroid release in culture. The enhancement of ovarian steroid synthesis in cocultures with the mesonephros at certain ages might be due either to increased substrate production and/or increased enzymatic activity. The lowering of steroids seen at different ages might be due to mesonephric steroid binding. The mesonephros appeared to influence the male and female rabbits differently at the same ages.

A sporadic case of delayed implantation after in-vitro fertilization in the human?

A possible case of delayed implantation after in-vitro fertilization (IVF) is described. The patient was sterilized in 1981, and made fertile again by tubal anastomosis in 1988. In 1990 and 1992 the patient had two right-sided tubal pregnancies, the first was treated with prostaglandin instillation, the second with salpingectomy. In connection with the salpingectomy in 1992, the left tube was observed to be constricted in the middle part and with phimosis of the ostium. In 1994 three IVF embryos were transferred, but 15 days after the transfer, serum human chorionic gonadotrophin (HCG) was negative (< 10 IU/ml). Seven weeks after the embryo transfer, menstruation was still missing, and the serum HCG was now positive (329 IU/ml). Subsequent ultrasound scans were compatible with an intrauterine pregnancy, progressing normally, but 5 weeks delayed compared with the oocyte aspiration. The pregnancy was successfully carried to term. Such a long delay in detection of HCG, in association with a normal pregnancy, has not been described in the literature before.

The nucleotide sequence of the tnpA gene of Tn21.

The nucleotide sequence of the tnpA gene of Tn21 is presented. The transposase encoded by this gene is exactly the same length (988 amino acids) as the Tn501 transposase (4), and shows 72% homology overall with this protein, with greater homology towards the C-terminus. The sequence of the transposase is discussed in the context of the evolution of Class II transposable elements and of the characteristics of the enzyme's action.