Importance of planning ovulation induction therapy in systemic lupus erythematosus and antiphospholipid syndrome: A single center retrospective study of 21 cases and 114 cycles*

https://doi.org/10.1053/sarh.2002.37212Get rights and content

Abstract

Objective: To analyze the results and complications of ovulation induction therapy (OIT) in women with systemic lupus erythematosus (SLE) and/or the antiphospholipid syndrome (APS). Methods: A retrospective study of 21 women followed in a single tertiary-referral French center who underwent 114 OIT cycles with or without in vitro fertilization and embryo transfer (IVFET). Results: Before OIT, SLE was present in 6 women, APS in 3, SLE-related APS in 3, and discoid lupus in 1. Eight women had no identified disease and underwent 36 cycles of OIT. Diagnosis (SLE, n = 3; primary APS, n = 5) was made after OIT complication: spontaneous abortion (n = 5), SLE flare (n = 2), and thrombophlebitis (n = 1). Five women with known disease intentionally concealed their history from their gynecologists and underwent 34 cycles. Forty-four cycles were planned in 11 women, in 3 of them after complications of prior OIT performed without particular therapy and monitoring. Eighteen pregnancies occurred, which ended in 9 live births, 4 fetal deaths, and 5 embryonic losses. The pregnancy rate was higher with gonadotropin and/or gonadotropin-releasing hormone analog (GnRHa) (25% of cycles) than with clomiphene (4% of cycles, P <.0001). When the gynecologists did not know the underlying disease, three-quarters of pregnancies induced by OIT with IVFET ended in embryonic losses or fetal deaths. In contrast, 6 of 7 pregnancies induced by planned OIT with IVFET ended in live births (P <.0001). Phlebothromboses were observed only with gonadotropin treatment. The SLE flare rate was higher with gonadotropin and/or GnRHa (27% of cycle) than with clomiphene (6%, NS). It also was higher (30%) when the gynecologists did not know the underlying disease than in the planned procedures (10%, NS). Conclusions: The OIT may precipitate SLE or APS. A careful review of the patient's history and appropriate laboratory tests should be undertaken before OIT. Clomiphene complications are rare. When gonadotropins are prescribed, preventive anti-inflammatory therapy should be considered in women with SLE, in addition to heparin and/or anti-aggregant therapy in patients with asymptomatic anti-phospholipid antibodies or prior thrombotic events. Semin Arthritis Rheum 32:174-188. Copyright 2002, Elsevier Science (USA). All rights reserved.

Section snippets

Patients

We retrospectively reviewed the records of 21 consecutive women with SLE and/or APS who underwent OIT with or without attempted IVFET. Data of four cases (cases 10, 12, 17, 18) reported previously (5) were augmented during a longer follow-up period. Nineteen patients fulfilled the modified American College of Rheumatology criteria for SLE (9). Patients 2 and 4 fulfilled only three criteria.

Lupus anticoagulant (LA) was detected by activated partial thromboplastin time (PTT), diluted

Clinical characteristics at OIT onset

Mean age at OIT was 32 ± 4 years (range, 26-41). Mean infertility duration was 4 ± 3 years (range, 1-10). Primary infertility occurred in 10 women, and secondary in 11. Two women with APS had each one prior normal untreated pregnancy that occurred several years before thrombophlebitis while using estrogen-containing contraception. Four women had a history of fetal death, complicated by preeclampsia in one. Another woman had preeclampsia with premature delivery. Four women had histories of

Discussion

We followed 21 women with SLE or APS who underwent OIT for primary or secondary infertility. Five of them subsequently became pregnant spontaneously. This underlines the fact that infertility duration should always be taken into account for indication of OIT.

Conclusions

The OIT may complicate or reveal SLE or APS, and gynecologists should be aware of this danger. A careful history and screening is mandatory before OIT, based on obstetrical, thrombotic, hematologic, articular, or skin anomalies, especially if gonadotropin use is considered.

Complications of clomiphene therapy are rare.

On the contrary, when gonadotropins are prescribed, a preventive anti-inflammatory therapy should be considered in SLE patients, in addition to either heparin or anti-aggregant

Acknowledgements

The authors thank Pr Aumaitre (Clermont-Ferrand), Drs Audibert (Clamart), Bercau (Paris), Bulwa (Paris), Janse-Marec (Levallois-Perret), Le Hello (Caen), Loraillere (Bar le Duc), Priollet (Paris), Rolet (Neuilly), Rouffet (Chartres), Ruckstuhl (Beauvais), and Tournier (Besançon).

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    *

    Address reprint requests to Du Le Thi Huong, MD, PhD, Department of Internal Medicine, Groupe Hospitalier Pitié-Salpêtrière, 83 bd de l'Hôpital, 75013 Paris, France.

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