Assisted Reproductive Therapy Effective in SLE Patients: Study
But the therapy may have other issues in systemic lupus erythematosus
Almost half of women with systemic lupus erythematosus (SLE) who underwent assisted reproductive therapy (ART) became pregnant, and 83.3% of them had a successful delivery, a large retrospective study shows.
Only a small number of women experienced lupus flares, but ART was linked to a higher incidence of premature delivery, and with babies having a low weight at birth. ART also was linked to a higher risk of gestational diabetes, a pregnancy complication that causes the mother’s blood sugar levels to rise to unhealthy levels.
“The safety and efficacy of ART is assured in lupus patients with stable disease,” the researchers in China wrote. “Premature delivery, GDM [gestational diabetes mellitus], and LBW [low birth weight] infants remain to be important issues.”
The study, “Pregnancy outcomes in patients receiving assisted reproductive therapy with systemic lupus erythematosus: a multi-center retrospective study,” was published in the journal Arthritis Research & Therapy.
In the past, women with SLE traditionally were advised to avoid having children due to potential complications that included miscarriage, stillbirth, preeclampsia (high blood pressure during pregnancy), and premature birth.
With diagnostic and therapeutic advances, women with SLE are no longer discouraged from pregnancy. Still, estimates show that more than 50% of SLE patients have fewer children than what they would like.
Anti-phospholipid antibodies, common in patients with SLE, may promote the formation of blood clots in small blood vessels that impair embryo implantation. Also, immunosuppressive medications used to manage lupus, namely cyclophosphamide, have been linked to infertility.
ART has been a common strategy to improve fertility in the general population.
However, “the application of ART in lupus patients remains to be a matter of ongoing debate,” the researchers wrote.
Ovulation induction therapy (OIT), a type of ART, may lead to lupus flares and blood clot formation. Despite the potential risks, ART has been carried out successfully in lupus patients.
However, the majority of studies focused on fertility assistance in SLE have been conducted in a very small number of patients, which hinder the draw of generalized conclusions.
Much larger study
Now, researchers in China conducted a multicenter retrospective study to evaluate the safety, efficacy, and pregnancy complications of ART in SLE patients.
In total, they reviewed data from 142 women with SLE who were followed during one or more cycles of ART at three hospitals in the region of Guangzhou, China, from January 2013 to October 2022.
Women with SLE who became pregnant naturally — a total of 280 — also were included and served as controls. They were divided into two groups: those who had planned their pregnancy and those who did not.
Of the 142 women who underwent ART, 66 became pregnant, with a total of 72 pregnancies. Of these, six were ectopic pregnancies, which occur when the fertilized egg implants outside the womb. This yielded a clinical pregnancy rate of 46.5%. Patients had a mean age of 34 years at their first pregnancy, with a median SLE disease duration of 42.5 months (about three-and-a-half years).
A total of 27 women (40.9%) had histories of adverse pregnancy, including 17 spontaneous abortions (25.8%), 11 ectopic pregnancies (16.7%), seven therapeutic abortions (10.6%), and one case of preeclampsia (1.5%).
Before becoming pregnant, 39.4% of women were taking glucocorticoids, 6.1% were on cyclosporin A, 86.4% on hydroxychloroquine, 15.2% on low-dose aspirin, and 10.6% on low molecular weight heparin.
Primary infertility occurred in 20 patients (30.3%), while secondary infertility was seen in 46 (69.7%). Primary infertility is the term used when a pregnancy was never achieved, while secondary infertility is the term used when a woman is unable to conceive after giving birth before.
The main causes for infertility included obstruction of the fallopian tubes (25.8%), followed by premature ovarian failure (13.6%) — a condition in which the ovaries stop working normally before the age of 40. The fallopian tubes are the reproductive structures in a woman’s body that connect the ovaries to the uterus.
OIT was conducted in 60 pregnancies (83.3%), and in vitro fertilization (IVF) in 58 (80.6%). Another ART technique called intracytoplasmic sperm injection (ICSI) was performed in seven pregnancies (9.7%), and intrauterine insemination (IUI) in two (2.8%).
In IVF, mature eggs are collected from the ovaries and fertilized by sperm in the lab. ICSI involves directly injecting a sperm into an egg to ensure ferilization, and in IUI, sperm is placed directly in the uterus around the time of ovulation to facilitate fertilization.
Overall, 60 pregnancies (83.3%) ended successfully with the delivery of 65 babies, including five pairs of twins. Delivery by C-section occurred in 42 pregnancies (63.6%).
Premature delivery was the most frequent complication — occurring in 21 patients (31. 8%) at an average gestation time of 36.8 weeks. Gestational diabetes was reported in 15 patients (22.7%).
A total of 10 women (15.2%) experienced lupus flares. In most cases, flares were mild (40%) or moderate (50%) in severity.
A total of 20 babies (30.8%) had low-body weight, and two (3.1%) had very low body weight. Most of these babies (63.6%) were born prematurely. Ten (15.4%) were transferred to the intensive care unit after delivery, but no neonatal lupus or fetal heart problems were observed.
Women in the ART group were older (mean age 34) when compared to controls in the planned pregnancies (mean 31.1 years) and unplanned pregnancies (mean 28.4 years) groups.
Also, a history of adverse pregnancy was more frequent among women in the ART group compared with the control groups. Women who received ART also were more likely to develop gestational diabetes.
However, disease flares and fetal loss were significantly lower in women in the ART group when compared with controls.
Delivery time happened earlier, on average, for women in the unplanned pregnancies group (34.8 weeks) compared with those in the ART group (36.8 weeks), and the average birth weight was lower in the unplanned pregnancies group compared with ART (mean 2,298 grams vs. 2,653 grams — 5 pounds and 5.8 pounds, respectively).
Overall, these findings support that “ART is safe and yields satisfactory outcomes in lupus patients with stable disease for more than one year,” the researchers wrote.
“Maternal and fetal APOs [adverse pregnancy outcomes] are comparable with planned pregnancy and reduced significantly compared with unplanned pregnancy,” they wrote.
However, “the incidences of premature delivery, GDM [gestational diabetes mellitus], and LBW [low body weight] infants” were higher in the ART group.