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PubMed2001

Polycystic ovarian syndrome and the risk of spontaneous abortion following assisted reproductive technology treatment.

BACKGROUND: A high proportion of infertile patients have polycystic ovarian syndrome (PCOS) with a reportedly greater risk of spontaneous abortion. Because of the close link between PCOS and obesity and the independent association of obesity with poor pregnancy outcomes, it is important to distinguish the possible confounding effect of body mass index (BMI) or other variables from that of PCOS. This study aims to determine the effect of PCOS status on the risk of spontaneous abortion with adjustment for body mass and several other confounding factors in a large cohort of pregnant infertile women. METHODS: The patients (n = 1018) were treated in a tertiary infertility centre. Their PCOS status was determined by standard criteria and their BMI had been taken less than 1 year before the pregnancy. Patients whose PCOS status or BMI measurements were not assessed were excluded. Student's t-test or chi2 test were used to test the difference between the PCOS and non-PCOS groups while a multivariate logistical regression model was used to assess the effect of PCOS, BMI and other confounding factors. RESULTS: Overall, the incidence of PCOS was 37% in this cohort. The overall incidence of spontaneous abortion in the study population was 21%. Univariate analysis showed that women with PCOS had a significantly greater risk of spontaneous abortion compared with non-PCOS women (25 versus 18%, P < 0.01). However, using multivariate logistic regression analysis this effect was reduced to a non-significant level [odds ratio (OR) = 1.10, 95% confidence interval (CI) 0.85-1.36] after adjusting for obesity and patients/treatment combination factor, and to nil after adjusting for all confounding factors considered in this study (OR = 0.98, 95% CI 0.75-1.28). CONCLUSION: The results of this study suggest that the higher risk of spontaneous abortion observed in women with PCOS is likely to be due to their high prevalence of obesity and the type of treatment they receive.

Abortion, Spontaneous↗
PubMed1990

Development of assisted conception.

Advances in assisted human conception in the last twenty years were founded on the detailed knowledge of the mammalian reproductive cycle gained in the earlier years of this century. Several lines of study coincided in the 1960's, including the use of ovarian stimulants to regulate follicle growth, oocyte maturation and ovulation, fertilization and embryonic growth in vitro, and the introduction of safer and better methods of laparoscopy. A combination of these techniques with embryo replacements in the uterus permitted the introduction of IVF for the alleviation of infertility. In turn, these methods were extended to other forms of assisted conception, including GIFT, which gave a wider choice of methods for the treatment of specific causes of infertility. Advances during the last decade include rapid progress in the use of ultrasound, the introduction of the LHRH agonists in new forms of stimulation, embryo cryopreservation, and micromanipulative techniques on oocytes and embryos for the alleviation of male infertility and the diagnosis of genetic disease in preimplantation embryos.

Female↗
PubMed1990

Outcome of pregnancies resulting from assisted conception.

With the increasing practice of assisted conception, the health of the resulting children is becoming an increasingly important issue. Experience with four thousand children conceived by IVF or GIFT indicates that multiple pregnancy, which frequently results from assisted conception, is the main determinant of complications during pregnancy and of the health of the children at the time of birth. Overall malformation rates are similar to those in the country as a whole. There are, however, still insufficient numbers of children studied to draw firm conclusions about the risk of specific types of malformations. This will require the continued monitoring of children resulting from assisted conception, and the continued co-operation of many individuals and centres practising assisted conception.

Adult↗
PubMed1996

Incidence of spontaneous abortion in clomiphene pregnancies.

The purpose of this study was to determine whether the use of clomiphene results in a higher incidence of spontaneous abortion than occurs naturally in subfertile patients. Reproductive outcomes of 1744 clomiphene pregnancies were compared to outcomes of 3245 spontaneous pregnancies in a prospective study. Abortion was classified as clinical if a sac was seen on ultrasound or if it occurred after 6 gestational weeks, and as preclinical if a quantitative human chorionic gonadotrophin (HCG) was > or = 25 mIU and no sac was seen or abortion occurred earlier. The overall incidence of abortion was higher for clomiphene pregnancies (23.7%), compared with spontaneous pregnancies (20.4%) (P < 0.01). Preclinical abortions were increased by clomiphene for all ages (5.8 versus 3.9%, P < 0.01) and for age > or = 30 years (8.0 versus 4.9%, P < 0.001), but not for age < 30 years (3.7 versus 3.0%). Clinical abortions were increased by clomiphene for age < 30 years (15.9 versus 11.2%) (P < 0.01), but not for age > or = 30 years (20.1 versus 22.3%) or all ages (18.0 versus 16.4%). Clinical abortions occurred 22% less often following clomiphene compared with spontaneous pregnancies for patients with luteal insufficiency (18.3 versus 23.6%, P < 0.05). We conclude that the increase in abortion due to clomiphene is small and may be related to different causes for women aged < 30 and > or = 30 years, and also that clomiphene may decrease clinical abortions in patients with luteal insufficiency.

Abortion, Spontaneous↗
PubMed1995

The stages at which human fertilization arrests: microtubule and chromosome configurations in inseminated oocytes which failed to complete fertilization and development in humans.

The goal of fertilization is the union of one, and only one, sperm nucleus with the female pronucleus within the activated oocyte. For this to occur successfully, several events must transpire, including the incorporation of the entire spermatozoon into the oocyte, the completion of meiotic maturation with the extrusion of the second polar body, the metabolic activation of the previously quiescent oocyte, the decondensation of the sperm nucleus and the maternal chromosomes into the male and female pronuclei respectively, and the cytoplasmic migrations of the pronuclei, which bring them into apposition. Defects in any of these events are lethal to the zygote and might prove to be causes of infertility. In this study, the microtubules and DNA were imaged in inseminated human oocytes that had been discarded as unfertilized. The presence and number of incorporated sperm tails were also documented using a monoclonal antibody specific for the post-translationally modified acetylated-alpha-tubulin found in the tail, but not the oocyte, microtubules. An analysis of 211 oocytes from failed in-vitro fertilizations from 58 patient couples resulted in the determination of several previously undetectable phases at which fertilization arrests: (i) metaphase II arrest; (ii) arrest after the successful incorporation of the spermatozoon, (iii) arrest after the formation of the sperm aster; (iv) arrest during mitotic cell cycle progression; and (v) arrest during meiotic cell cycle progression. Data on polyspermy and arrested embryonic development are also presented. These results have implications for the diagnosis and treatment of female, as well as male, infertility.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Cycle↗
PubMed1989

Human sperm--egg interactions and their disorders: implications in the management of infertility.

The present era of infertility management is characterized by an increasing interest in defects of sperm--egg interactions. When the spermatozoon meets the egg, it must first react with the enveloping coat which controls sperm access to the cell surface of the oocyte. Adequate sperm motility is a major condition for penetration through the egg investments. The ability of spermatozoa to respond to physiological stimuli by a timely acrosome reaction is another necessary prerequisite for this event, as well as for sperm fusion with the oocyte. The clinical significance of current laboratory tests evaluating different aspects of gamete function is discussed and a practical guide is given for their indication and interpretation and for the use of their results in choosing rational therapy.

Acrosome↗
PubMed1989

Programming of ovarian stimulation with norethindrone acetate in IVF/GIFT cycles.

Twenty patients were given norethindrone acetate (NET) to program the initiation of controlled ovarian hyperstimulation and to coordinate follicular aspiration with surgery to obtain spermatozoa from the husband. Patients received NET, 10 mg/day orally, starting between days 2 and 4 of the cycle. The duration of NET therapy varied from 9 to 37 days. The mean time of onset of vaginal bleeding, after cessation of NET, was 2.9 +/- 0.7 days. Ovarian stimulation was carried out with a combination of a luteinizing hormone releasing hormone analog, follicle-stimulating hormone and human menopausal gonadotrophin. The day of human chorionic gonadotrophin (HCG) administration ranged from day 8 to day 15 of the cycle (10.1 +/- 1.7). On the day of HCG injection, the mean E2 level was 2188 +/- 1126. The mean number of follicles aspirated was 18.4 +/- 9.9 per cycle. The mean number of oocytes collected per cycle was 15.5 +/- 8.5. There was no correlation between duration of NET suppression and the number of days of gonadotrophin therapy needed to reach HCG administration. The large number of oocytes retrieved is probably related more with the fact that the patients represented a group with a purely male factor of infertility, than by the specific drug protocol utilized. Our results demonstrate that the ovarian response to gonadotrophin stimulation was not affected by NET administration. The main advantages of the use of this drug for cycle control are that its administration is oral, simple and inexpensive.

Adult↗
PubMed1989

The relationship of abnormal semen parameters to male fertility.

To what extent do standard semen parameters reflect male fertility? A review of many studies over the last 35 years relating pregnancy rate to sperm counts in 'fertile' and 'infertile' couples indicates that standard semen parameters, though much maligned of late, are useful in evaluating the degree of 'male factor' in an infertile couple. However, 'male factor' is quite compatible with fertility in a couple if the wife is very fertile. Oligoasthenozoospermia is, unfortunately, for the most part, an untreatable condition. Yet, vigorous treatment of the wife may still result in pregnancy despite very poor semen quality. Higher sperm counts in an infertile couple are associated with higher pregnancy rates. But in the majority of infertile couples in whom the sperm count is poor, female factors also exist that prevent conception. If the wife were very fertile, she would have become pregnant despite her husband's oligozoospermia, and they would never have seen a physician for infertility. Thus, pregnancy can be achieved with very low sperm counts either by treatment of the wife, IVF, GIFT or ZIFT procedures.

Female↗
PubMed1990

Comparison between different pre-treatment techniques for sperm recovery prior to intrauterine insemination, GIFT or IVF.

An attempt was made to compare different pre-treatment techniques in 16 normal and proven fertile and 30 subnormal and hitherto infertile semen samples. The techniques used were (i) standard, (ii) layering, (iii) discontinuous Percoll density gradient and (iv) albumin columns. Percoll gradient was most effective in separating a high fraction of progressive motile spermatozoa (75 and 57% in normal and subnormal semen samples, respectively). The albumin columns, as well as the standard techniques, were equally effective in recovering 45 and 24% respectively of progressive motile spermatozoa in normal and subnormal semen samples. The layering method was the least effective of the four techniques (4% recovery in normal and subnormal semen samples). In cases of contamination with inflammatory cells, the standard and layering methods were significantly (P less than 0.001) more advantageous than isolations with Percoll gradient and albumin columns. The percentage of ideal forms of spermatozoa recovered from a normal semen sample was significantly higher with the standard (P less than 0.01), layering (P less than 0.05) and Percoll gradient (P less than 0.05) techniques. In subnormal samples, only the Percoll gradient gave a significantly (P less than 0.02) higher percentage of ideal forms, whereas the other techniques were less effective. The significance and practical use of the various pre-treatment techniques are discussed in relation to the characteristics of the pre-treatment semen sample.

Cell Separation↗
PubMed1990

The probability of multiple births when multiple gestational sacs or viable embryos are diagnosed at first trimester ultrasound.

The live birth outcome when multiple gestational sacs were diagnosed at first trimester ultrasound was reviewed in 227 twin, 43 triplet and five quadruplet pregnancies. When two gestational sacs were present, the probability of delivering twins was 63% for maternal age less than 30 and 52% for maternal age greater than or equal to 30. With three gestational sacs, the probability of a triplet birth was 45% for maternal age less than 30 and 18% for maternal age greater than or equal to 30. When two viable embryos were present, the probability of a twin birth was 90% for maternal age less than 30 and 84% for maternal age greater than or equal to 30. With three viable embryos, the probability of a triplet birth was 90% for maternal age less than 30 and 44% for maternal age greater than or equal to 30. Two gestations resulting from ovulation induction with clomiphene citrate were more likely to result in twin delivery at term, compared to spontaneous twin gestations (P = 0.012). These findings may be useful in the treatment and management of patients when multiple gestations are diagnosed early in pregnancy.

Adult↗
PubMed1991

Effects of in-vitro exposure to HCG on subsequent HCG-responsiveness of human granulosa cells obtained following treatment with GnRH analogue and gonadotrophins: an in-vitro model for luteal phase support.

The pregnancy rate in patients undergoing assisted conception treatment following pituitary desensitization with GnRH analogue and ovarian stimulation with gonadotrophins has been reported to be higher when ovarian function is supported in the luteal phase by exogenous human chorionic gonadotrophin (HCG). In the present study, we have examined the effects of culturing monolayers of granulosa cells, collected from such patients at oocyte retrieval, for various time intervals in the presence or absence of HCG on their subsequent ability to secrete progesterone (P4) either spontaneously or in response to further challenge with HCG. When cultured in the absence of HCG, granulosa cells demonstrated a rapid decline in both the spontaneous P4 secretion rate and the ability to secrete P4 in response to HCG. Maintenance in the presence of HCG inhibited the rapid decline in ability to secrete P4 spontaneously and also significantly enhanced the ability to respond to subsequent HCG stimulation. These results suggest that HCG support in the luteal phase in GnRH analogue-treated patients may have a cellular basis for its action both in maintenance of P4 secretion and also in rendering the corpus luteum more sensitive to rescue by conceptus-derived HCG.

Buserelin↗
PubMed1991

Attitudes of donors and recipients to gamete donation.

An anonymous questionnaire was circulated at two gamete donation clinics to survey the attitudes of donor insemination patients (n = 71; 89% response rate), sperm donors (n = 52; 85% response rate) and ovum donors (n = 5; 63% response rate) to the release of medical records with non-identifying information, or with identifying information of the donor involved. The majority of established sperm donors agreed to the release of medical records with or without identifying information. In the subset of potential sperm donors 85% would not enter a sperm donation programme unless anonymity was maintained, but 60% would agree to the release of non-identifying medical records. Sixty per cent of recipients of donated spermatozoa would agree to the release of medical records with identifying information of the donor, but 85% stated that they would not tell their children of their genetic origin. There is a significant difference between the attitudes of potential sperm donor recruits to these questions and those of established donors and recipients of donated spermatozoa. In conclusion, the results of this survey show that although established sperm donors would continue to donate spermatozoa if their status of anonymity was withdrawn, recruitment of new donors would be significantly reduced. This would be to the detriment of gamete donation programmes and to the subfertile couples who request this form of treatment.

Attitude↗