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Chorionic gonadotrophin secretion by human blastocysts.

Abnormal embryos that arose in our in-vitro fertilization programme were cultured in serum-free minimum essential medium (MEM), and those that developed into blastocysts were cultured up to day 14 after fertilization to study the influence of various supplements on chorionic gonadotrophin (CG) secretion. Human cord serum, at a concentration of 1%, was found to be one of the most effective stimulants for initiating and maintaining CG production. A mixture of insulin+transferrin+selenium (ITS) stimulated CG secretion in serum-free MEM, although the output of hormone began to decline after approximately 3 days. Platelet-derived growth factor (PDGF) produced a similar response to ITS. Stimulation of blastocyst CG secretion in the absence of serum could also be induced with 8-bromo-cAMP. All stimulants were able to evoke CG secretion in day 7-8 blastocysts. These studies have shown that multiple factors were capable of inducing CG production by early blastocysts. On the basis of these and other studies it was postulated that receptors for insulin, transferrin and PDGF were expressed in preimplantation blastocysts.

Blastocyst↗

Utility of gonadotropin-releasing hormone agonists in programs of ovarian hyperstimulation with intrauterine insemination.

The GnRH agonists have practical and theoretic advantages for adjunctive use in ovulation induction. The IVF cycles demonstrate a decrease in the cancellation rate, an increase in the ease of scheduling, and an increase in the number of oocytes obtained per retrieval when GnRH agonists are employed. Other advantages, such as an improvement in the fertilization and cleavage rate, an increased length of the luteal phase, and an increased pregnancy rate, are suggested but not universally accepted. The utility of adding GnRH agonists to human menopausal gonadotropin-intrauterine insemination cycles is similarly in dispute. Although controlled ovarian hyperstimulation with both human menopausal gonadotropins alone and in conjunction with GnRH agonists have produced pregnancies when coupled with intrauterine insemination, it was demonstrated that there was a significantly greater pregnancy rate per cycle with the use of a GnRH agonist in a recalcitrant infertile population. Others did not substantiate this improvement in pregnancy rate per cycle in their patient population of regularly ovulating women undergoing their first controlled ovarian stimulation cycle either with or without GnRH agonist therapy. This suggests that women with ovulatory dysfunction, and particularly women who previously have not responded to therapy with human menopausal gonadotropin therapy, will reap the most benefits from the addition of a GnRH agonist to their ovulation induction regimen. The addition of a GnRH agonist to controlled ovarian hyperstimulation is a highly effective method of inducing pregnancy in a recalcitrant infertile population. Patients who did not conceive with human menopausal gonadotropins-intrauterine insemination may conceive with GnRH agonist-human menopausal gonadotropins-intrauterine insemination therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

Endometriosis and assisted reproductive technologies.

The association between endometriosis and infertility is well established, and different mechanisms have been postulated to cause infertility depending on the stage of endometriosis. Controlled ovarian hyperstimulation improves pregnancy outcome for minimal to mild endometriosis; however, there are no randomized controlled studies of this technique in patients with severe disease. Further, ART appears to have an overall beneficial effect for all stages of endometriosis. Based on the current staging system, several studies have not been able to demonstrate a significant difference in true outcomes for different stages of the disease. The limitations of these studies have been discussed above. Similarly, the effect of endometriomas when considered independent of the stage is still unclear. In addition to ART, pretreatment with GnRH analogues or surgical intervention may be beneficial and needs to be addressed in randomized controlled studies. It is evident that we urgently need large randomized studies to answer several questions about the treatment of endometriosis-associated infertility with ART. Although our current practice is based primarily on retrospective observational studies and small randomized studies, the overall impact on pregnancy outcome is beneficial.

Endometriosis↗

Transcervical tubal cannulation: a review.

Rapid progress has been made in the last 10 years regarding minimally invasive access to the human fallopian tube. Coaxial catheter systems are being used with hysteroscopy, fluoroscopy, ultrasonography, and tactile sensation to cannulate the fallopian tube transcervically with consistent success. Uterotubal obstruction viewed at the time of hysterosalpingogram can often be successfully cannulated with intrauterine pregnancies resulting. This review surveys all available published series of transcervical tubal cannulation with discussion of methodology, success in establishing patency, and the resultant pregnancy rates. It also describes how this technology has been applied to the intratubal deposition of gametes and embryos, direct visualization of the tubal epithelium, (falloposcopy), and contraception. Collectively, these techniques are defining tubal pathology more precisely, allowing us to prescribe the proper therapy.

Clinical Trials as Topic↗

The cryopreservation of donor semen by a simplified method: use in an IVF and GIFT programme.

The cryopreservation of semen used in assisted reproduction procedures was carried out exclusively by a simplified method in which a mixture of semen and cryoprotectant was contained in 1-ml tuberculin syringes and plunged directly into liquid nitrogen. Donor semen samples halved and frozen in syringes and in straws in a controlled-rate freezer showed no significant difference in post-thaw motility (P = 0.217) or survival (P = 0.217) after 30 min. However, after 180 min the survival rate showed a significant reduction in syringes (P = 0.045). A significant difference (P less than 0.00008) in the rate of fertilization of oocytes was seen in IVF cycles using frozen-thawed donor sperm (58/142, 42%) when compared to fresh sperm from husbands (2315/3926, 59%). A significant reduction (P less than 0.00005) in fertilization rate was also observed in the case of supernumerary oocytes in GIFT cycles with the cryopreserved donor sperm (29/132, 22%) compared to the husbands' sperm (239/514, 46%). However, the pregnancy rate following IVF and embryo replacement was the same after fertilization with fresh sperm (75/351, 21%) as opposed to frozen sperm (3/14, 21%). Furthermore, a higher pregnancy rate was observed in GIFT with frozen donor sperm (9/19, 47%) than with fresh sperm from husbands (28/103, 27%), though this was not statistically significant (P = 0.079). These results show this simplified methods of semen cryopreservation to be effective when used in an IVF and GIFT programme, giving pregnancy rates comparable to fresh normospermic semen samples. The method is simple, quick and inexpensive.

Cell Survival↗

In vitro fertilization failure: identification of gamete defects by investigation of sperm-zona pellucida binding capacity of unfertilized oocytes.

The objective of the study was to determine whether fertilization failure was due to spermatozoal or oocyte factors. Twenty-five unfertilized oocytes from 12 IVF/GIFT couples showing total or partial fertilization failure were evaluated for sperm zona binding potential under hemizonaeassay (HZA) conditions. Hemizonae were separately incubated with a sperm sample from the husband and that of a fertile control. Tight sperm binding to hemizonae was assessed. First, among the 12 patients, results showed a possible zona defect thought to be the cause of fertilization failure in five cases. Second, in two cases, fertilization failure was possibly caused by poor sperm binding potential of spermatozoa. Third, in two cases, fertilization failure was possibly caused by an oocyte defect, and fourth, three cases showed a mixture of possible causes. The results stress the need to develop a sequential analytic programme for those couples with repeated total or partial fertilization failure.

Adult↗

Radiological abnormalities in children born as a result of assisted conception.

Over 15,000 children are born each year as a result of the various techniques of assisted conception. In 1991, there were 2083 live births in Australia and New Zealand as a result of these techniques. Radiological abnormalities relating to the increased rate of prematurity, a probable increase in the risk of congenital malformations and a number of cases of neural crest tumours seen in these infants will be presented.

Australia↗

Attitudes towards gamete donation among couples undergoing in vitro fertilization.

The attitudes of 234 anonymous couples undergoing in vitro fertilization toward sperm and oocyte donation were explored by questionnaire. All the questionnaires were returned of which 222 (95%) were complete and analysed. A high proportion of couples found the use of donor sperm acceptable for therapeutic, diagnostic and treatment purposes (77%, 90% and 97% respectively) and 72%, 84% and 90% respectively were willing to donate oocytes for these purposes. Of potential oocyte donors 41% would agree to nonanonymous donation, 12% would wish to meet the recipient couple and although only 4% wanted to choose the recipient, a quarter of the couples would prefer a relative or friend as the recipient. Provision of nonidentifying information about the donor to the recipient couple was acceptable to almost 70% whereas 40% found giving the same information to the child acceptable.

Adult↗

Spontaneous fetal reduction in multiple gestations assessed by transvaginal ultrasound.

OBJECTIVE: To assess the occurrence of disappearance of one or more of the fetuses in pregnancies which start as multiple gestation. DESIGN: Observational study. SETTING: Infertility section, Rambam Hospital, Haifa. SUBJECTS: 88 women with multiple gestations, established after ovulation induction (54 twin, 26 triplet, five quadruplet, and three quintuplet) and diagnosed by transvaginal ultrasound at 5-6 weeks, in all of whom absorption of at least one gestation sac was detected at follow-up ultrasound scan. INTERVENTIONS: Follow-up by serial transvaginal and later abdominal ultrasound scan throughout pregnancy. RESULTS: Of the 54 twin gestations, 51 ended in the birth of a singleton and three in miscarriage. Of the 26 pregnancies starting as triplets, 12 ended in singleton births, 12 in twins and two miscarried. The five quadruplet gestations resulted in one singleton birth, one set of twins, two triplets, and one ended in late miscarriage. Of the three quintuplet pregnancies, two resulted in the birth of triplets, one of them after spontaneous, the other after iatrogenic fetal reduction. In the third quintuplet pregnancy, one fetus vanished spontaneously and another was subject to iatrogenic reduction, two fetuses survived and were liveborn. Of the 221 fetuses identified 107 (48%) vanished spontaneously. CONCLUSION: Iatrogenic fetal reduction should be delayed until 12 weeks gestation in quadruplet or higher multiple gestations, but is probably not indicated in twin and triplet gestations.

Adult↗

Higher multiple births and the modern management of infertility in Britain. The British Association of Perinatal Medicine.

OBJECTIVE: To assess prospectively the number of triplet and higher multiple births born in 1989 and their methods of conception. To assess obstetric factors and the effect of these pregnancies on neonatal medical services. DESIGN: All consultant paediatricians received a monthly card asking whether they had been involved in the management of triplet and higher multiple pregnancies delivered after 22 weeks gestation. Detailed questionnaire sent to those giving a positive response. SETTING: British Paediatric Surveillance Unit organized mailings to all members of the British Paediatric Association working in the British Isles. SUBJECTS: 156 pregnancies resulting in 482 babies (143 triplets, 12 quadruplets and 1 quintuplet set). These data were compared to nationally collected OPCS data. MAIN OUTCOME MEASURES: Method of conception, obstetric performance, neonatal outcome. RESULTS: Of the 156 pregnancies, 47 (31%) were conceived naturally, 52 (34%) had ovarian stimulation (usually with clomiphene or gonadotrophins) 37 (24%) had IVF and 17 (11%) GIFT. All quadruplet and quintuplet pregnancies were established after assisted reproduction. Mothers who had had IVF were significantly older than those who had ovulation induction alone. The median gestation at birth was 33 weeks. Overall 181 (40%) of the babies required intensive care for a median duration of 5 days. The perinatal mortality of the triplets alone and quads and quins together was 70 and 104 per 1000 respectively. CONCLUSIONS: Assisted reproduction is the major cause of triplets and higher multiple births and ovarian stimulation is the single most important technique currently in use. These babies are very likely to be born pre term and make considerable demands on neonatal intensive care facilities.

Adult↗