A favorable outcome of pregnancies in women with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome.

OBJECTIVE: To study the outcome of pregnancies in women with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome treated with the standard treatment regimes including intravenous immunoglobulin (IV Ig). METHODS: Forty three patients with recurrent pregnancy loss associated with antiphospholipid syndrome diagnosed before pregnancy and subdivided into primary (18) and secondary (25) subgroups were closely monitored all through pregnancy with serial blood tests and ultrasonography until the pregnancy ended in miscarriage or delivery. The patients were treated with low-dose aspirin and heparin and or steroids and IV Ig given to some selected patients. The maternal and fetal outcomes were analysed. RESULTS: The mean age of the patients in the primary subgroup (24.60 +/- 4.30) years was significantly lower than the mean age of the secondary recurrent pregnancy loss group (31.50 +/- 4.50) years, (p < 0.0001). 85.00% of all the previous miscarriages were in the first trimester. There was no significant difference in the incidence of live births in the primary (77.80%) and secondary (84.00%) groups, (p > 0.05); the babies were of normal birth weight. The incidence of caesarean section in the primary and secondary groups, 22.23% and 12.00% respectively, were not significantly different (p > 0.05). Intravenous immunoglobulin added to the standard therapy resulted in 100% live births. Maternal complications were negligible. CONCLUSIONS: The fetal and maternal outcome of pregnancies in patients with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome were virtually identical and quite satisfactory. Intravenous immunoglobulin added to the standard therapy resulted in excellent fetal and maternal outcome, although its definitive role will have to wait for the outcome of randomised trials.

'Early coasting' in patients with polycystic ovarian syndrome is consistent with good clinical outcome.

BACKGROUND: Coasting can be an effective strategy for the prevention of severe ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. However, OHSS may still occur in cases of excessive follicular response (i.e. >10 follicles/ovary and serum estradiol (E(2)) concentration >3000 pg/ml). Furthermore, prolonged coasting may result in a reduction of the oocyte retrieval rate and embryo quality. This pilot study investigates the potential of withholding gonadotrophins at an earlier stage, with the intention of minimizing these risks. METHODS: Gonadotrophin injections were withheld for a fixed period of 3 days once the leading follicle was 15 mm, whilst continuing pituitary down-regulation in 102 obese patients with polycystic ovarian syndrome (PCOS) in whom there was evidence of excessive ovarian follicular response (>10 follicles per ovary and serum E(2) >1500 but <3000 pg/ml). The events of ovarian stimulation, embryological and clinical outcomes were studied prospectively. RESULTS: The mean number of ampoules (75 IU per ampoule) of high purity (hp) FSH was 23.2. The mean serum E(2) level on coasting day 1 was 1943.7 and 2169.2 pg/ml on the day of HCG administration. Normal fertilization and cleavage rates were obtained despite early withdrawal of hpFSH in the obese PCOS patients, being 73.9 and 87.7% respectively. The clinical pregnancy rate was 45.1%. There were no cases of severe OHSS. Four patients suffered pregnancy-associated late-onset moderate OHSS. CONCLUSIONS: This pilot study suggests that withholding gonadotrophins at an earlier stage in patients with excessive ovarian follicular response at anticipated risk of developing severe OHSS in the course of ovarian stimulation is consistent with good embryological and clinical outcome in IVF and ICSI treatment cycles.

The aetiology and pattern of recurrent pregnancy loss.

The aims of this study were to determine the aetiological factors and the pattern of recurrent pregnancy loss in Kuwait. Ninety consecutive patients attending the special recurrent miscarriage clinic were studied prospectively. A comprehensive history of all previous miscarriages and pregnancies, past medical and gynaecological events were established. A physical examination was performed. Extensive investigations were performed. Pregnancies which occurred during the study were monitored carefully. The mean age of the patients was 30.46+/-6.04 years. The patients were subdivided into the groups of secondary (57%) and primary (43%) recurrent miscarriages. Eighty-five per cent of all previous miscarriages occurred in the first trimester. The main aetiological factors were uterine anomaly 2.2%, chromosome anomaly (parental) 2.2%, PCOS, infections and other miscellaneous factors 21.1%, positive antiphospholipid antibodies 33.3% and unexplained in 35.6%. The overall live birth rate was 82% and maternal morbidity was low. Positive antiphospholipid antibodies are the most frequently associated cause of recurrent pregnancy loss in Kuwait.

Effect of repeated doses of dexamethasone on the incidence and severity of respiratory distress syndrome in multifetal gestation between 24 and 34 weeks.

The objective of the study was to evaluate the effects of antenatal corticosteroid therapy in multiple pregnancy on the incidence and severity of respiratory distress syndrome (RDS). Twenty-two women with twin, 12 with triplet and 2 with quadruplet pregnancies and an emergency group of 20 mothers with twin pregnancies, who only had one course of dexamethasone, were compared with controls. Corticosteroid therapy was associated with a reduction in moderate to severe RDS in all groups (twins p < 0.01, triplets and quadruplets p < 0.008) and the emergency group with dexamethasone therapy (p < 0.036) when compared to their individual controls. Dexamethasone reduced the duration of stay in the neonatal intensive care unit of the emergency twin group (p < 0.01). Neonatal birth weights were significantly less in all groups treated with repeated doses in comparison to the controls.

Serum oestradiol and progesterone concentrations during prolonged coasting in 15 women at risk of ovarian hyperstimulation syndrome following ovarian stimulation for assisted reproduction treatment.

Serum oestradiol and progesterone concentrations were examined for up to 7 days after withholding gonadotrophins whilst continuing pituitary down-regulation in 15 women at serious risk of severe ovarian hyperstimulation syndrome (OHSS) (serum oestradiol >6000 pg/ml and >15 follicles per ovary). Serum oestradiol concentrations rose on day 1 of coasting in all but two of the 15 women before falling, the decrement being in the order of 40% on each day. This observation permits a rational basis for the estimation of frequency of serum oestradiol measurements and duration of coasting. The trends and rates of fall of serum oestradiol do not seem to predict the occurrence of moderate and severe OHSS, being similar in the six women who developed OHSS compared with nine women without OHSS. The trends in progesterone concentrations were unrelated to any aspects of the clinical outcome.

Influence of position and length of uterus on implantation and clinical pregnancy rates in IVF and embryo transfer treatment cycles.

In a prospective study of 807 consecutive women shown to have an apparently normal uterus after hysterosalpingography, hysteroscopy or pelvic ultrasonography prior to IVF or intracytoplasmic sperm injection (ICSI) and embryo transfer, the position and length of the uterine cavity was measured routinely at a pre-treatment mock transfer procedure. The apparent length of the uterine cavity was <7 cm in 128 women (group 1), 7-9 cm in 594 women (group 2) and >9 cm in 85 women (group 3). The uterus was noted to be retroverted in 38. 2% (308) women. The embryo transfer catheter was advanced to 5 mm from the uterine fundus based on the previously determined cavity length in all the embryo transfer procedures at 48 h after oocyte collection. Implantation and clinical pregnancy rates were not significantly different with respect to position of the uterus, difficulties encountered in passage of the catheter, mean age of the women, aetiology or duration of infertility or embryology events. An apparently greater cavity length was seen in older and/or parous women, but the difference was not statistically significant. Although the highest implantation and clinical pregnancy rates were seen in women with a cavity length of 7-9 cm (group 2) the differences were not statistically significant: group 1, 18.9 and 36. 7%; group 2, 21.0 and 46.5%; and group 3, 17.3 and 32.9% respectively. The incidence of ectopic pregnancy per reported clinical pregnancy was highest in group 1 women, being 14.9% (7/47) in comparison with group 2 (1.8%, 5/276) and group 3 (0%, 0/27) (P: < 0.0005), suggesting that the size of the uterus is a critical factor in the aetiology of ectopic pregnancy in IVF/ICSI-embryo transfer.

Prophylactic antibiotics and endocervical microbial inoculation of the endometrium at embryo transfer.

Prophylactic antibiotics administered routinely to women at the time of oocyte retrieval were associated with a reduction in positive microbiology cultures of embryo catheter tips 48 h later in 78.4% of patients. The implantation and clinical pregnancy rates were significantly lower (9.3% vs 21.6%, p<0.001; 18.7% vs 41.3%, p<0.01) in the women with positive microbial catheter-tip cultures.

Early unilateral follicular aspiration compared with coasting for the prevention of severe ovarian hyperstimulation syndrome: a prospective randomized study.

Thirty women undergoing in-vitro fertilization or intracytoplasmic sperm injection considered to be at high risk of ovarian hyperstimulation syndrome (OHSS) were randomly allocated to have early unilateral follicular aspiration (EUFA) (group 1) or coasting (group 2) when the serum oestradiol concentration was >6000 pg/ml and there were more than 15 follicles each of >/=18 mm diameter in each ovary. EUFA was performed in group 1 at 10-12 h after the human chorionic gonadotrophin (HCG) trigger injection and human menopausal gonadotrophin (HMG) were withheld for 4.9 +/- 1.6 days until serum oestradiol concentrations fell below 3000 pg/ml when HCG was administered. The mean total dose and duration of administration of HMG were similar in groups 1 and 2 (48.3 +/- 17.4 and 50.2 +/- 16.5 ampoules; 13.7 +/- 2.2 and 14.1 +/- 3.2 days respectively). The mean serum oestradiol concentrations (9911 pg/ml versus 10 055 pg/ml) and number of follicles (43.3 versus 41.4) seen in both ovaries on the day of HCG administration in group 1 and on the day coasting was commenced in group 2 were also similar. After coasting, the mean serum oestradiol concentration on the day of HCG administration in group 2 was lower than in group 1 (1410 pg/ml versus 9911 pg/ml; P < 0.001). The mean serum progesterone concentrations on the day of HCG administration in both groups were similar, and fell in all women in group 2. The mean number of oocytes retrieved and percentage of oocytes retrieved per follicle punctured was significantly higher in group 1 (15.4 +/- 2.1 versus 9.6 +/- 3.2, P < 0.001; 91.4 +/- 4.4% versus 28.3 +/- 3.7%, P < 0.001 respectively). The fertilization and embryo cleavage rates were similar in both groups. Clinical pregnancy was diagnosed in 6/15 (40%) patients in group 1 and in 5/15 (33%) patients in group 2, while four women in group 1 and three in group 2 developed severe OHSS.

Antiphospholipid antibodies in infertile couples with two consecutive miscarriages after in-vitro fertilization and embryo transfer.

Of 682 women who had undergone in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with embryo transfer, 84 were successful on two occasions, with 16 of these resulting in miscarriage before 20 completed weeks. Antiphospholipid antibodies (APA) were estimated by enzyme-linked immunosorbent assay in these women (group 1) and compared to two control groups: 42 fertile women with three or more miscarriages (group 2) and 60 women with primary infertility undergoing IVF or ICSI (group 3). An apparently higher prevalence of seropositivity was seen in group 1 women (25%) compared to the group 3 women (6.6%) and it was similar to that seen in group 2 women (21.4%). Therefore the recommendation that women with two consecutive miscarriages after IVF or ICSI should have APA estimations performed routinely may be justified.

Maternal and perinatal outcomes of multiple pregnancy following IVF-ET.

OBJECTIVE: To analyze the course of pregnancy and perinatal outcome in 31 twins, 22 sets of triplets and five quadruplet clinical pregnancies following conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) procedures and in relation to 58 singleton pregnancy following the same procedure. METHODS: Retrospective analysis of maternal and neonatal medical records of 58 singleton, 31 twin, 22 triplet and five quadruplet pregnancies diagnosed at 7-8 weeks gestation following 561 embryo transfer procedures in 628 oocyte collections at the IVF Center in the Maternity Hospital, Kuwait from July 1994 to December 1996. RESULTS: The clinical pregnancy rate in 628 cycles proceeding to oocyte collection was 32.6%, there being 58 singletons (50.6%), 31 twins (33.5%), 22 triplets (10.8%) and five quadruplets (2.5%). Early complicated outcomes included 47 miscarriages (23.7%), four ectopic pregnancies (1.9%) and one hydatidiform mole. The spontaneous fetal reduction rate was 20.6% in twin, 45.5% in triplet and 40% in quadruplet pregnancies. There was a significantly higher maternal and neonatal complication rate in the triplet group compared to singletons and twins, including threatened miscarriage, pre-eclampsia, antepartum hemorrhage, longer hospital stay and preterm labor. The chance of operative delivery was higher in high-order multiple pregnancy (HOMP). The major neonatal complications were related to prematurity. Neonatal morbidity and mortality were significantly higher in the triplet group. The need for admission to the Special Care Baby Unit (SCBU) and the Neonatal Intensive Care Unit (NICU) was significantly higher in HOMP. However, there were no statistically significant differences in the perinatal mortality in relation to the degree of HOMP. CONCLUSION: Maternal complications, perinatal and neonatal morbidity after 2 years activities in the IVF Center have been reviewed leading to changes in policies of management, notably a reduction in the number of embryos transferred.

Pregnancy rates after intracytoplasmic sperm injection in relation to sperm recovery techniques.

PURPOSE/METHODS: Clinical outcome after intracytoplasmic sperm injection (ICSI) was evaluated in relation to three techniques of sperm recovery, mini-Percoll, simple concentration, and centrifugation and washing. RESULTS: Whereas fertilization and embryonic cleavage rates were similar in the three groups, the rates of implantation and clinical pregnancy were statistically significantly higher following sperm recovery by the techniques of mini-Percoll and centrifugation and washing.

Timed unilateral ovarian follicular aspiration prior to administration of human chorionic gonadotrophin for the prevention of severe ovarian hyperstimulation syndrome in in-vitro fertilization: a prospective randomized study.

Unilateral ovarian follicular aspiration 6-8 h prior to trigger administration of human chorionic gonadotrophin (HCG) was performed or not in 31 women at serious risk of ovarian hyperstimulation syndrome (OHSS) after ovarian stimulation for in-vitro fertilization (IVF)-embryo transfer or intracytoplasmic sperm injection (ICSI) in this prospective randomized study. Unilateral follicular aspiration was performed in 16 women (group 1) matched for age, indication for fertility treatment, and the amount and duration of gonadotrophin exposure with 15 women not receiving aspiration treatment (group 2). There was a statistically significantly (P < 0.001) lower mean number of oocytes obtained from group 1 women (14.9 +/- 1.8 vs 22.6 +/- 2.4). The fertilization (53.2 +/- 2.6 vs 65.5 +/- 1.35%) and embryonic cleavage (91.3 +/- 2.1 vs 90.2 +/- 1.75%) rates were similar in both groups. OHSS occurred in women from both groups (group 1: 25% vs group 2: 33.3%) being severe OHSS in two women from group 1 and one from group 2. We conclude that unilateral ovarian early follicular aspiration prior to HCG trigger administration does not reduce the occurrence of severe OHSS in women at risk.

Mimicking the high levels of activity of a large in-vitro fertilization unit leads to early success at the commencement of an in-vitro fertilization and embryo transfer programme.

Infertile couples seeking treatment will endeavour to obtain the highest standards of care at a conveniently located centre. The success rated of a centre would also be an important concern. The busier in-vitro fertilization (IVF) units (> 400 cycles per year) have substantially higher pregnancy rates than those carrying out < 300 cycles per year. We report our experiences at the IVF centre, Maternity Hospital, Kuwait of mimicking the high level of activity of a large IVF unit. Infertile couples were treated in groups of 30-35 every 4-6 weeks. Patients in each group had menstrual cycles synchronized to their luteal phase using progestogens. Thereafter they were down-regulated with gonadotrophin-releasing hormone agonist (long protocol). Oocyte retrieval and embryology activities were concentrated and completed in 7-10 days in each group. This episodic high level of activity was aimed at mimicking that of a busy large IVF centre, although continuous in the latter. The overall results in terms of fertilization cleavage, implantation and clinical pregnancy rates were similar to those obtained in large IVF units. The clinical pregnancy rate per cycle was 25.8-39.1% in IVF and 46.1% in intracytoplasmic sperm injection.

Incidence of microbial growth from the tip of the embryo transfer catheter after embryo transfer in relation to clinical pregnancy rate following in-vitro fertilization and embryo transfer.

A total of 110 consecutive women was studied prospectively at the time of transcervical embryo transfer following conventional in-vitro fertilization and intracytoplasmic sperm injection procedures. Microbiological cultures were performed on endocervical swabs and embryo transfer catheter tips. Positive microbial growths were observed from endocervical swabs in 78 (70.9%) women and from catheter tips in 54 (49.1%) women. The clinical pregnancy rates were 57.1% in the group of patients without growth and 29.6% in the group with positive microbial growth from catheter tips. As microbial contamination at embryo transfer may influence implantation rates, prospective studies are justified to determine whether eradication of endocervical micro-organisms is possible and whether their eradication will improve implantation rates.

Outcome of assisted reproduction technology in infertile couples of consanguineous marriage.

PURPOSE: The outcome of pregnancies resulting from assisted reproduction technology does not seem to differ from the outcome of those arising from spontaneous natural conception. METHODS: There is increased risk of chromosomal abnormality in spontaneous natural pregnancies resulting from consanguineous marriage, with consequent higher rates of miscarriage, stillbirth, and congenital abnormalities. RESULTS: This study has shown a trend of an increased miscarriage rate (but not statistically significant) in pregnancies achieved in infertile couples of consanguineous marriages by assisted reproductive technology. CONCLUSIONS: Selecting embryos for transfer on the basis of their morphology does not appear to reduce the risk of chromosomal abnormality in these couples.