Efficacy and safety of long-acting GnRH agonists in in vitro fertilization and embryo transfer.

The introduction of gonadotrophin-releasing hormone (GnRH) agonists combined with gonadotrophins is considered to be one of the most significant events in the development of in vitro fertilization and embryo transfer (IVF-ET) programmes. This article reviews the use of GnRH agonists in IVF-ET programmes and the efficacy and safety of long-acting GnRH agonists. The use of agonists results in higher clinical pregnancy rates, more supernumerary embryos for cryopreservation and allows convenient programming of oocyte recovery. There are different types of agonist and ovarian stimulation protocol available for clinical use. Recent meta-analysis of the Cochrane database has demonstrated the superiority of the long protocols over the short and ultra-short protocols for GnRH agonist use in IVF and GIFT. The depot injection offers increased clinical and patient compliance and improves efficacy of pituitary downregulation. However, compared with short-acting agonists, the depot preparations are associated with a longer period of stimulation and higher doses of gonadotrophins. To date, there is no evidence of an increased risk of pregnancy wastages or teratogenicity in human pregnancies exposed to long-acting agonists.

The case for routine HIV screening before IVF treatment: a survey of UK IVF centre policies.

The case for routine human immunodeficiency virus (HIV) screening of all couples seeking assisted reproductive treatment is so strong that it should be made obligatory for all couples entering IVF programmes to be given information about HIV transmission, and offered testing. In August 1999, questionnaires regarding routine HIV screening of couples seeking IVF treatment were sent to the medical directors of the 74 licensed assisted conception units in the UK. Of the 45 (60.8%) centres who responded, 19 (42.2%) routinely screen both partners for HIV antibodies, 25 (55.5%) do not screen and one centre selectively screens high-risk patients. There was no significant difference in the proportion of centres that routinely carried out screening with regards to the unit size: six out of 13 (46.2%) small units compared with 13/32 (40.6%) large units. In all, 17 centres (37.8%) rated HIV screening as essential, nine (20%) as desirable, 11 (24.4%) as not required, while eight (17. 8%) centres did not comment. Of the 19 centres that have a routine screening policy, 18 have management protocols in the event that the test is positive. Of these 18 centres, 12 adhere rigidly to the protocol, while five centres adhere to the protocol with few exceptions and the remaining one uses its protocol for guidance only. The main reasons for not employing routine HIV screening were: the lack of cost effectiveness, low prevalence of HIV infection in their population, necessity for and cost of counselling, uncertainty about the need for screening and potential delay to start of treatment.

Termination of pregnancy after conception with donor oocytes and donor spermatozoa: case report.

Two couples, each suffering from longstanding primary subfertility due to severe oligoasthenoteratozoospermia in the male partner and perimenopause in the female, were referred to Bourn Hall Clinic for assisted conception treatment. Both couples received independent counselling prior to being accepted onto our programme. Both women conceived following embryo transfer. The embryos were created from (separate) donor oocytes and donor spermatozoa, and three and two embryos were transferred respectively. The first recipient conceived a triplet pregnancy, while the second conceived a twin pregnancy. Both felt unable to cope with their multiple pregnancies and declined further counselling. Both were offered elective fetal reduction; however, both declined and both decided to terminate their pregnancies. Both patients underwent termination of pregnancy, despite being advised against it. The reasons couples may opt for termination of their much-wanted pregnancies, after a protracted period of infertility, intensive and expensive infertility treatment and despite the counselling they receive before, during and after their treatment, are discussed.

Maternal serum screening for Down syndrome in women aged 40 years and over.

Two hundred and thirty-nine women aged 40 years were booked for delivery at Kettering General Hospital from 1992 to 1997. Six women were not eligible for the triple test (TT) as they booked too late. Eighty-eight women declined TT. The reasons were; fear and anxiety about the risk of miscarriage associated with amniocentesis if the test result were a high risk (70.5%), worries about the false negative result associated with the TT (20.5%) and reluctance to terminate the pregnancies if the fetus were abnormal (9%). One hundred and forty-five women (62.2%) elected for TT of whom 91 (62.8%) had received a high risk results. Of the women who received a high-risk result 61/91 (67%) had an amniocentesis. The study provides an accurate probability of receiving a high risk TT screening in women aged 40 years and highlights the need for a more sensitive screening test or a less invasive diagnostic test for the detection of Down syndrome.

In-vitro fertilization and embryo transfer in women aged 40 years and over.

The decline of fertility with age and its possible causes are discussed; in particular the effect of ageing of oocytes and the uterus, and the effect of the ageing processes on the results of in-vitro fertilization (IVF) and embryo transfer in women aged > or =40 years. The role of prestimulation testing in older women is considered together with the importance of screening and counselling these patients about the likelihood of achieving a live birth. The potential problems that they may face should they become pregnant are reviewed, together with the role of oocyte donation as an alternative treatment for patients with reduced ovarian reserve. Possible ways of improving the chances of achieving a live birth in older women using their own oocytes are reviewed, including the use of more effective stimulation protocols, assisted embryo hatching and co-culture and high order embryo transfer. The outcome of pregnancies in older women and some of the ethical problems relating to their treatment are also discussed.

Astonishing fertility from a single oocyte recovery.

A 36 year old patient underwent in-vitro fertilization (IVF) and embryo transfer. Three embryos were transferred to her uterus and eight spare embryos were cryopreserved. The patient conceived a quadruplet pregnancy and delivered two boys and two identical twin girls by Caesarean section at 30 weeks gestation. The couple subsequently donated their cryopreserved embryos to the embryo donation programme for the use of other couples. Two agonadal patients received these cryopreserved-thawed embryos, each in a hormone replacement cycle. Both conceived, one has safely delivered twins and the other conceived a twin pregnancy, one of the fetuses has vanished and the other is progressing normally. The overall embryo implantation rate was seven out of nine (78%).

The prediction of ectopic pregnancy after in-vitro fertilization and embryo transfer.

Data from 135 patients who suffered ectopic pregnancies and from 135 patients who progressed to singleton deliveries after in-vitro fertilization and embryo transfer have been analysed retrospectively. The ectopic pregnancies represent all such cases observed at Bourn Hall Clinic between 1983 and 1993. The delivered group was randomly selected from the same time period. The ectopic pregnancies included 20 heterotopic, eight ovarian and six bilateral tubal pregnancies; the remainder were singleton tubal pregnancies. The aim of this study was to identify the variables which differed systematically for the two groups of patients and to explore whether such variables could be used to predict ectopic pregnancy at an early stage. The mean plasma concentration of human chorionic gonadotrophin and progesterone for the ectopic pregnancy group was significantly lower than that for the singleton delivery group (P < 0.001). However, there was such a degree of overlap that it was impossible to devise a cut-off concentration for either hormone which would offer a clinically useful predictor of ectopic pregnancy. Nevertheless, using the discriminant function analysis of these data, together with the history of pelvic inflammatory disease, we could predict up to 90% of cases of ectopic pregnancy by day 23 after embryo transfer, long before ultrasound imaging would be useful.

Heterotopic pregnancies after in-vitro fertilization and embryo transfer.

A total of 20 cases of heterotopic pregnancy were encountered among 2650 clinical pregnancies (0.75%) resulting from in-vitro fertilization/embryo transfer at Bourn Hall Clinic (Cambridge, UK) during the period July 1984-July 1993. The aetiology of heterotopic pregnancy in the series is multifactorial, with tubal damage as the main factor. Transvaginal ultrasonography showed a high sensitivity for making correct diagnoses of heterotopic pregnancies compared with transabdominal ultrasonography (93.3 versus 50.0%). The mean plasma human chorionic gonadotrophin (HCG) concentration on day 13 after embryo transfer was similar to those of uncomplicated intrauterine pregnancies and hence was of no diagnostic value. The serial plasma HCG concentrations of patients who delivered were significantly higher than for those who aborted their intrauterine pregnancies (P < 0.01), although the sample of data available was too small to make firm inferences. It does appear that serial HCG concentrations may have a predictive value of fair accuracy regarding the outcome of the intrauterine pregnancy in heterotopic pregnancies. The clinical presentations of the 20 cases at first examination were quite variable, with 45% (9/20) of patients asymptomatic. Tubal pregnancy in one patient resolved spontaneously, two cases were treated by an injection of potassium chloride into the gestational sac and the remaining 17 cases were treated by salpingectomy. In 10 patients the intrauterine pregnancy resulted in live birth and the remaining 10 patients aborted spontaneously.

Analysis of the incidence and risk factors associated with ectopic pregnancy following in-vitro fertilization and embryo transfer.

Ectopic pregnancy is a well known complication of in-vitro fertilization (IVF) and embryo transfer. From March 1983 to December 1993, 3000 clinical pregnancies were achieved at Bourn Hall Clinic, including 135 ectopic pregnancies (4.5%). Of these ectopics 20 were heterotopic, eight ovarian, six bilateral tubal and the remainder were singleton tubal pregnancies. The main risk factor identified in the series was a history of pelvic inflammatory disease (P < 0.001). The data also showed that ectopic pregnancy is at present more prevalent among patients in whom tubal damage is the reason for treatment. There was slight statistical evidence (P = 0.05) that patients having ectopic pregnancies received a higher volume of culture medium than those having normal deliveries. There was also an apparent trend (P = 0.07, not significant) that high progesterone/oestradiol ratio on the day of embryo transfer was associated with ectopic pregnancy. There was no statistical evidence of association between ectopic pregnancy and a history of ectopic pregnancy, abortion, still birth, termination of pregnancy, neonatal death, tubal surgery, ovarian stimulation protocol, plasma concentration of oestradiol, luteinizing hormone and progesterone, number of oocytes retrieved, number or quality of embryos transferred, administration of general anaesthesia for embryo transfer, and the number of patent Fallopian tubes. Awareness of the risk factors associated with ectopic pregnancy plays an important part in the early diagnosis of this potentially fatal condition.

Tuberculous infertility and in vitro fertilization.

OBJECTIVES: Our purpose was to assess the outcome of in vitro fertilization and embryo transfer in tuberculous infertility and to study the factors associated with success or failure of treatment. STUDY DESIGN: Ten patients with tuberculous infertility underwent 22 cycles of in vitro fertilization and 9 cryopreserved-thawed embryo transfers at Bourn Hall Clinic. All patients underwent endometrial assessment by ultrasonography. Four patients had preliminary hysteroscopy, endometrial biopsy, and Doppler uterine blood flow studies. RESULTS: Six clinical pregnancies resulted in three live births in three patients and one current pregnancy in a fourth patient. There was one ectopic pregnancy and one twin pregnancy that aborted spontaneously at 14 weeks. The patients who had trophic endometrium achieved pregnancy at a rate of 42.9% (six of 14) (per embryo transfer) compared with 0% (none of 14) if the endometrium was atrophic. CONCLUSION: In vitro fertilization and embryo transfer offers the only realistic treatment for tuberculous infertility. Preliminary assessment of the endometrium is helpful in assessing prognoses in these cases.

High rates of pregnancy after long-term down-regulation of women with severe endometriosis.

OBJECTIVE: The purpose of this study was to determine the effects of pituitary down-regulation for several months on the outcome of in vitro fertilization treatment in women with severe endometriosis. STUDY DESIGN: A total of 84 patients with severe endometriosis (grades III and IV) were recruited in a semirandomized prospective study; 69 of these were controls who were given a short protocol with gonadotropin-releasing hormone agonist followed by human menopausal gonadotropin and human chorionic gonadotropin to induce follicular growth. Fifteen treated patients underwent down-regulation for 2 to 7 months and then human menopausal gonadotropin and human chorionic gonadotropin to induce follicular growth. Twenty nonpregnant controls after in vitro fertilization were treated in a similar manner. RESULTS: The pregnancy rates were much high per embryo transfer, 18 of 42 (42.8%), especially in patients in whom in vitro fertilization was carried out during the fourth month of down-regulation. Pregnancy rates in the control group were 17 of 134 (12.7%) (p < 0.001). CONCLUSION: Higher rates of pregnancy are achieved after in vitro fertilization that follows long-term down-regulation in women with extensive endometriosis.

Endometrial ossification: a cause of secondary infertility. Report of two cases.

Two cases of endometrial ossification with secondary infertility are reported; pelvic ultrasonography suggested an intrauterine foreign body in one case. Hysteroscopy was necessary to make the correct diagnosis and to remove the bony fragments from the two cases. One patient conceived naturally after the bony fragments were removed.

Primary ovarian pregnancy after in vitro fertilization and embryo transfer: report of seven cases.

We have reported seven cases of ovarian pregnancy from among 116 EPs and 2,745 clinical pregnancies achieved after IVF and ET at Bourn Hall Clinic. All were associated with lower than normal serial levels of serum hCG and P. Transvaginal US scanning correctly made the diagnosis of ectopic gestation in all cases, and in five, ovarian pregnancy was suspected on the scan findings. Three patients were asymptomatic, whereas four complained of lower abdominal pain with or without vaginal discharge or bleeding. All patients were treated conservatively; four had ovarian wedge resection and three ovarian cystectomy.

Comparative trial between an ultra-short and long protocol of luteinizing hormone-releasing hormone agonist for ovarian stimulation in in-vitro fertilization.

A total of 312 patients with tubal infertility participated in a prospective randomized study comparing two regimens of ovarian stimulation with a luteinizing hormone-releasing hormone agonist (buserelin) and human menopausal gonadotrophin (HMG). Half of the patients were given an ultra-short treatment protocol when the agonist was administered on days 2, 3 and 4 of the stimulated cycles; the other half were given a long protocol when the agonist was administered from the mid-luteal phase of the cycle preceding the treatment cycle. The mean number of HMG ampoules used per patient was significantly higher in the long protocol. No significant differences were found between the two groups in the incidence of cancelled cycles, failed oocyte recovery, mean number of oocytes recovered per patient, complete failure of fertilization and the fertilization and embryo cleavage rate. More patients undergoing the long protocol had supernumerary embryos cryopreserved and successful deliveries.