This study was undertaken to explore whether intervention with heparin and aspirin (H/A) in selected patients undergoing in-vitro fertilization (IVF) and embryo transfer could improve fecundity rates. Specifically, it explored the possibility that women diagnosed with organic pelvic disease who demonstrated antiphospholipid antibodies (APA) could benefit from H/A administration in a similar manner to that used in patients with recurrent pregnancy loss. We used an enzyme-linked immunosorbent assay for six different phospholipids to identify patients who expressed APA before they underwent IVF/embryo transfer. This study was confined to the first IVF/embryo transfer cycle that followed assessment of APA status and accordingly, the number of IVF/embryo transfer cycles corresponds with the number of patients treated. APA seropositive patients were treated with aspirin, 81 mg orally q.d., and heparin 5000 IU s.c. b.i.d., beginning on day 1 of controlled ovarian stimulation. The endpoint for success was a live birth or an ultrasound confirming fetal cardiac activity (a viable pregnancy). The prevalence of APA in patients diagnosed with organic pelvic disease (53%) was much higher than in those without female pathology (14%). The administration of H/A to APA seropositive patients significantly (P < 0.05) improved the viable pregnancy rate (49%) compared to the untreated APA seropositive group (16%). The viable pregnancy rate for APA seropositive women treated with H/A was also significantly (P < 0.001) higher than for untreated APA seronegative patients (27%). We conclude that all women undergoing IVF/embryo transfer should be tested for APA prior to initiating ovarian stimulation and those with APA seropositivity should be treated with H/A.

Over a 4 year period ending 1 January 1995, 51 women scheduled for in-vitro fertilization (IVF) and embryo transfer were inadvertently severely overstimulated with menotrophins, as evidenced by the development of > 29 ovarian follicles in association with peak plasma oestradiol concentrations of > 6000 pg/ml. Accordingly, these women were at great risk of developing life-endangering complications associated with severe ovarian hyperstimulation syndrome (OHSS). Treatment involved withholding the administration of both menotrophins and human chorionic gonadotrophin for a number of days, while continuing gonadotrophin-releasing hormone agonist until the plasma oestradiol concentration fell to < 3000 pg/ml ('prolonged coasting'). The mean number of oocytes retrieved was 21.0, while the mean number of embryos transferred per procedure was 5.4. There were 21 clinical pregnancies (i.e. pregnancy rate of 41% per oocyte retrieval), 19 of which resulted in live births (i.e. a live birth rate of 37% per oocyte retrieval). Two pregnancies miscarried and there were four multiple gestations (three sets of twins and one set of triplets). None of the women developed severe OHSS. Prolonged coasting is an effective method of preventing the occurrence of severe OHSS without necessitating the cancellation of the IVF cycle or compromising success rates.

Cytotrophoblasts, purified from human term placentae, were cultured in the absence or presence of 8-bromo-cAMP or 8-bromo-cGMP. 8-Bromo-cAMP provoked a dose-dependent increase in the secretion of hCG and progesterone within 24 h. After 48 h, hCG secretion increased by more than 200-fold, and progesterone secretion increased nearly 5-fold. 8-Bromo-cGMP had no effect on hCG secretion. In culture in serum-supplemented medium, the mononuclear cytotrophoblasts aggregated and fused to form syncytia. This morphological transformation was not affected by 8-bromo-cAMP. Immunocytochemical studies of the alpha- and beta-subunits of hCG in control and 8-bromo-cAMP-stimulated cultures demonstrated that the cyclic nucleotide analog promoted the synthesis of both subunits in all cellular forms, including single mononuclear cells, cell aggregates, and syncytia. In serum-free medium, the cytotrophoblasts did not aggregate or form syncytia, yet they responded to 8-bromo-cAMP with an increase in hCG secretion. We conclude that the endocrine function of cytotrophoblasts can be stimulated by a cAMP-dependent mechanism which can be initiated independently of the formation of a syncytium.

The treatment of APA+ women with H/A alone improves IVF birthrates. This benefit is selective in that it does not apply in cases in which IgG- or IgM-related APAs are directed against PE or PS. In such cases, the addition of IVIg significantly improves the outcome.

We conclude that IVIg therapy significantly improves IVF success rates in ATA+ women.

IVF outcome is significantly improved when H/A and IVIG are administered to APA+ women with repeat IVF failures. APA- women do not seem to benefit from such treatment.

A total of 816 women who underwent 1332 cycles of ovarian stimulation for in-vitro fertilization and embryo transfer (IVF/ET) had sonographic assessments of the endometrium within 2 days of oocyte retrieval. Endometrial linings were classified on the basis of thickness and echogenicity, using a grading system described previously. Grades I and IIB ('poor') were associated with a 6% viable pregnancy rate (advanced beyond 12 weeks' gestation) compared with a 29% rate for Grade IIA ('optimal'). In a subset of 112 women with poor endometrial linings during natural cycles, eight out of 21 women (38%) under 40 years of age developed optimal linings following ovarian stimulation with menotrophins, while 19 out of 91 women (21%) aged 41-45 years converted to optimal linings. Twenty-two out of 47 women (44%) who failed to develop optimal endometrial linings following ovarian stimulation converted to Grade IIA during subsequent cycles of exogenous oestrogen replacement. The financial, emotional, and physical burden associated with IVF/ET demands that patients with poor endometrial linings following ovarian stimulation with menotrophins be counselled with regard to either cancelling their cycles of treatment, or having their embryos cryopreserved for transfer to the uterus during a subsequent hormonal replacement cycle.

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