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.

Transrectal electroejaculation combined with in-vitro fertilization: effective treatment of anejaculatory infertility due to spinal cord injury.

Infertility due to spinal cord injury (SCI) in young men is a frequent complication of their injury. When the simpler methods of management of the erectile and ejaculatory dysfunction that invariably follow the more severe types of SCI are not effective, then semen production by transrectal electroejaculation (TREE) combined with in-vitro fertilization (IVF) and embryo transfer is effective. A retrospective analysis is presented of data on the treatment and outcome of 35 couples who wished to have a family but in whom the male partner had suffered SCI. These 35 couples had 71 attempts at IVF with spermatozoa obtained following TREE. Normal fertilization and cleavage of the embryos occurred in 48.2% of the oocytes. Fresh embryos were transferred in 54 cycles and frozen-thawed embryos in 14 cycles. In all, 18 clinical pregnancies were achieved in 54 fresh and 14 frozen embryo transfer cycles, with a live birth rate of 16.5% (14/85) per treatment cycle started, 20.6% (14/68) per transfer cycle and 40.0% (14/35) per couple who started treatment, in a mean of 1.9 transfer cycles. We conclude that TREE combined with IVF and embryo transfer is an effective treatment for the infertility problems associated with SCI.

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%).

Risks for transmission of hepatitis C virus during artificial insemination.

OBJECTIVE: To identify risks of hepatitis C virus transmission by semen from infected donors. DESIGN: Case report. SETTING: Assisted fertility clinic. PATIENTS: Hepatitis C virus-infected semen donor and recipients of his donations. INTERVENTION: Testing for hepatitis C virus by serology and polymerase chain reaction. MAIN OUTCOME MEASURES: Detection of hepatitis C virus antibodies and viral RNA. RESULTS: Hepatitis C virus RNA was detected in the semen donation before but not after purification; none of the recipients of the donors samples were found to have antibodies to hepatitis C virus. CONCLUSIONS: Hepatitis C virus RNA can be detected in semen donations from infected donors; purification of donations before insemination significantly reduces the amount of viral RNA in the semen pellet.

Diagnosis, prevention and management of ovarian hyperstimulation syndrome.

The overall incidence of clinically important (moderate to severe) OHSS ranges from 1% to 10% of IVF cycles, but only a small proportion (0.5% to 2%) of the cases are severe. In extreme but rare cases, secondary complications such as deep vein thrombosis, respiratory distress and acute hepato-renal failure may occur. The main risk factors are the presence of polycystic ovaries, high ovarian response to superovulation therapy, the use of hCG to trigger the ovulatory process or for luteal phase support, and the endogenous production of hCG by an early pregnancy. The pathogenesis of OHSS is unknown, although the predominant biochemical mediator is thought to be the renin-angiotensin system. Ovarian stimulation should always be carefully monitored to identify those women at risk. In IVF cycles, the hCG injection should be withheld if the risk is judged to be too great. Some women will benefit from a policy of proceeding to collect oocytes, but electively cryopreserving any resulting embryos, thus allowing the ovarian stimulation cycle not to be wasted. The administration of albumin at the time of oocyte collection will reduce the chance of severe OHSS occurring. If a decision is made to proceed with oocyte recovery and embryo transfer, it may be advisable to give 5000 IU of hCG, rather than 10,000 IU, as the ovulatory trigger. Progesterone, and not hCG, should be given in the luteal phase. Women developing mild or moderate OHSS should be kept under outpatient surveillance to detect the minority that may progress to severe OHSS. Those with severe OHSS should be hospitalised for fluid and electrolyte management. Paracentesis under ultrasound guidance is recommended where there are tense ascites, but further surgical intervention should rarely be undertaken and only when there is good clinical evidence of ovarian torsion or haemorrhage.

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.

The benefits of low-dose aspirin therapy in women with impaired uterine perfusion during assisted conception.

The objective of this long-running study was to determine whether the addition of low-dose aspirin to a standard hormone replacement therapy (HRT) protocol improved uterine perfusion during assisted conception. A total of 99 women scheduled for frozen embryo replacement were studied. Endometrial preparation was with a standard buserelin/HRT protocol. Uterine perfusion was assessed by Doppler ultrasound and classified as impaired or normal. In their first attempts, those with impaired perfusion (group I, n = 37) received low doses of aspirin [150 mg (n = 26) or 300 mg daily (n = 11)], starting from day 13 of HRT. Women with normal perfusion (group II) did not receive aspirin. In subsequent attempts, those from group I were arbitrarily allocated to start aspirin on day 1 or day 13 of HRT, and 10 women from group II were arbitrarily selected to receive aspirin from day 1 of HRT. In group I, the cancellation (46 versus 36%) and pregnancy rates (15 versus 25%) in those who received 150 or 300 mg aspirin daily were similar. In those with cancelled first attempts, good perfusion was achieved in 82 versus 20% (P < 0.02) of subsequent attempts using aspirin from day 1 versus day 13 of HRT. Higher pregnancy rates (47 versus 17%) were achieved in those taking aspirin from day 1 of HRT. In group II, pregnancy rates were not statistically different in those who did or did not receive aspirin during their subsequent attempts (10 versus 35%). The addition of low-dose aspirin to a standard HRT protocol in women with impaired uterine perfusion is associated with improved blood flow and satisfactory pregnancy rates.

Outcome of inadvertent administration of a gonadotrophin-releasing hormone agonist (buserelin) in early pregnancy.

All women undergoing pituitary down-regulation before planned in-vitro fertilization (IVF) treatment in two IVF units were studied to assess the risks of and to pregnancies occurring inadvertently when gonadotropin-releasing hormone agonists (GnRHa) were used to achieve pituitary desensitization during the luteal phase prior to planned IVF treatment. In 2670 cycles, 25 women conceived (0.9% of cycles). Of these, three resulted in pre-clinical abortions (12%) but there were no clinical abortions, and 22 have ended with live births at term of apparently normal infants. Collation of these and other published data suggest that pregnancy outcome is not adversely affected by GnRHa administration in the luteal phase of the conception cycle.

High ovarian response in Yoruba African women during ovulation induction for assisted conception.

Fertile Yoruba women from western Nigeria have a much higher incidence of naturally conceived multizygotic twin and triplet pregnancies than Caucasians. The objective of the present study was to determine whether there are differences between infertile Yoruba and Caucasian women in terms of ovarian response in stimulate cycles for assisted conception. A total of 11 Yoruba women were scheduled for 14 in-vitro fertilization (IVF) and one gamete intra-Fallopian transfer (GIFT) cycles from 1990 to 1992. The Caucasian group consisted of 209 women scheduled for 213 IVF and 22 GIFT cycles during the same period. Buserelin, 500 micrograms subcutaneously daily, was started in the mid-luteal phase to achieve pituitary desensitization. Ovarian stimulation was with variable amounts of menopausal gonadotrophins. Human chorionic gonadotrophin (HCG) was given to trigger the ovulatory process. The Yoruba and Caucasian groups were similar in age and body weight, but significantly more Yorubas (45 versus 11%; P < 0.005) had ultrasound features of polycystic ovary syndrome (PCOS). The serum oestradiol concentration (3024 versus 2058 pg/ml; P < 0.05) and number of follicles > 14 mm in diameter (15.5 versus 9.5; P < 0.05) on the day of HCG were higher in the Yoruba group. The ovarian hyperstimulation syndrome (OHSS) was also more prevalent in the Yoruba group (20 versus 5%; P < 0.05). No difference was found in clinical pregnancy or embryo implantation rates. These results show a higher tendency toward exaggerated ovarian response in infertile Yoruba than Caucasian women, associated with a higher prevalence of PCOS. The risk of developing symptomatic OHSS is higher in Yoruba women.

Birth characteristics and perinatal outcome of babies conceived from cryopreserved embryos.

The objective of this retrospective study was to compare the birth characteristics and perinatal mortality of babies conceived from the use of cryopreserved embryos with those resulting from in-vitro fertilization (IVF) and fresh embryo transfer. A total of 232 consecutive births, one pregnancy termination and a total of 283 babies in the cryopreserved group were studied. The IVF data included 763 births, three terminations and 961 babies, based on a previous analysis. There was no difference in the incidence of twin (18 versus 19%) and triplet births (2 versus 3%) in the cryopreserved and IVF groups respectively. The mean gestational age and birthweight of singleton, twin and triplet births were not significantly different between the groups. No difference was found in the perinatal mortality rates. The incidence of major congenital malformations in the cryopreserved group (1%) was significantly lower than that in the IVF group (3%; P < 0.05). It is concluded that the birth characteristics of babies conceived from cryopreserved/thawed embryos are similar to those from fresh embryos. There are fewer congenital malformations in the cryopreserved group.

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.