[Show abstract][Hide abstract] ABSTRACT: The effect of mini-dose heparin/aspirin (H/A) alone vs. combined intravenous immunoglobulin G (IVIg) and H/A on in vitro fertilization (IVF) birthrates in women who test seropositive for antiphospholipid antibodies (APA+) was evaluated, as was the question of whether outcome is influenced by the gammaglobulin isotype(s) or the phospholipid (PL) epitope(s) to which the APAs are directed.
A case-control study was conducted in three phases, spanning a 4-year period, in a multicenter clinical research environment. Six hundred eighty-seven APA+ women, who were younger than 40 years and who each, completed up to three consecutive IVF/embryo transfer cycles within a 12-month period, were given either H/A alone or H/A in combination with IVIg. Birthrates relative to the type of immunotherapy (i.e., H/A alone and H/A with IVIg) and APA profile were the main outcome measurements.
In phase I, 687 women who tested APA+ to one or more PL epitopes underwent two or fewer IVF attempts for a total of 1050 IVF cycles. Four hundred seventy-seven (46%) births occurred in 923 IVF cycles in which H/A alone was administered. Twenty-two (17%) births occurred after 127 IVF cycles in which H/A was not administered. In phase II, 322 of 687 women tested positive for a single APA subtype. These subjects underwent up to two consecutive IVF attempts for a total of 521 IVF cycles while receiving H/A alone. The birthrate was significantly lower for women whose APAs were directed toward phosphatidylethanolamine (PE) or phosphatidylserine (PS) involving IgG or IgM isotypes than for women who had any other APA (17% vs. 43%). In phase III, 121 women who did not achieve live births after two consecutive IVF attempts in which H/A alone was administered received IVIg in combination with H/A during their third consecutive IVF cycle. The birth rate was 41% after these IVF cycles when anti-PS or anti-PE involving IgG or IgM isotypes were present, as compared with 17% when H/A alone was administered. The IVF outcome did not improve when IVIg was administered in association with any other single APA.
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.
American journal of reproductive immunology (New York, N.Y.: 1989) 09/1998; 40(2):74-82. · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 1) Does the administration of heparin and aspirin (H/A) in combination with intravenous immunoglobulin G (IVIG) improve in vitro fertilization (IVF) implantation and birth rates in patients with recurrent IVF failure? 2) Is the effect of such treatment related to the antiphospholipid antibody (APA) status of the patients concerned?
Subjects consisted of 89 women younger than 36 years of age whose infertility was a result of causes other than male infertility and who had experienced four or more failed IVF/embryo transfer procedures. Fifty-two women were APA+ (group A), and 37 were APA- (group B). All patients, regardless of their APA status, received H/A (5000 U sq bid), aspirin (81 mg po qd) from the inception of menotropin therapy along with IVIG (20 g) through a single infusion 3 to 10 days before egg retrieval.
Twenty-two (42%) of group A and 7 (19%) of group B patients achieved live births (P = 0.020).
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.
American journal of reproductive immunology (New York, N.Y.: 1989) 07/1998; 39(6):391-4. · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the effect of heparin/aspirin therapy alone vs. heparin/aspirin in combination with intravenous immuno-globulin (IVIg) immunotherapy on in vitro fertilization (IVF) outcome of patients who test positive for antithyroid antibodies (ATAs).
Eighty-two women younger than 40 years of age whose infertility was related exclusively to female causes were evaluated. All tested positive for organ-specific antithyroid antibodies (antimicrosomal and/or antithyroglobulin antibodies), but negative for antiphospholipid antibodies. Thirty-seven of these women (group A) received H/A alone, whereas 45 (group B) received heparin/aspirin in combination with IVIg.
Ten (27%) of women in group A and 23 (51%) of women in group B achieved live births after completion of a single IVF/embryo transfer cycle (P = 0.027).
We conclude that IVIg therapy significantly improves IVF success rates in ATA+ women.
American journal of reproductive immunology (New York, N.Y.: 1989) 04/1998; 39(4):223-5. · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Human Reproduction 01/1996; 10(12):3107-9. · 4.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Human Reproduction 01/1995; 9(12):2278-83. · 4.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ovum donation and in-vitro fertilization (IVF) surrogacy can help couples with difficult infertility problems achieve pregnancy. Most centres using oral oestrogens and oestradiol patches report pregnancy rates in the range of 30% per cycle. Parenteral oestradiol valerate has pharmacological properties that make it an attractive option for preparing the endometrium in the recipients undergoing these procedures. When the egg providers were under age 35 years, and using oestradiol valerate in the recipients, we achieved a 61% clinical pregnancy rate in 62 cycles. These improved results suggest that parenteral oestradiol valerate should be used to prepare the endometrium in recipients, and that the hormonal milieu of the endometrium plays an important role in the higher implantation rates obtainable in ovum donor and IVF surrogate cycles.
Human Reproduction 08/1993; 8(7):1145-7. · 4.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate a new method for preventing the life-endangering complications associated with inadvertent menotropin-induced severe ovarian hyperstimulation in patients undergoing in vitro fertilization and embryo transfer (IVF-ET).
Seventeen women each underwent a single cycle of controlled ovarian hyperstimulation with menotropins in preparation for IVF-ET. The indications for IVF-ET were tubal occlusion in nine, endometriosis in six, and unexplained infertility in two. The peak plasma estradiol (E2) concentration before hCG administration was greater than 6000 pg/mL and more than 30 ovarian follicles were detected by transvaginal ultrasound. Thus, life-endangering complications associated with severe ovarian hyperstimulation syndrome were highly likely to occur following hCG administration. Rather than cancel the cycle of treatment, menotropin therapy was discontinued and hCG administration was deferred for a number of days until the plasma E2 concentration fell below 3000 pg/mL ("prolonged coasting"), whereupon hCG was administered and egg retrievals and ETs were duly performed.
None of the women developed severe ovarian hyperstimulation syndrome. There were six viable pregnancies (35.2%), which proceeded normally.
This study indicates that "prolonged coasting" prevents severe ovarian hyperstimulation syndrome in severely overstimulated women undergoing IVF-ET, without necessitating cycle cancellation.
Obstetrics and Gynecology 07/1993; 81(6):1009-11. · 4.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Human Reproduction 04/1993; 8(3):347-9. · 4.67 Impact Factor