Demographic Data

We identified 32 patients with pSS undergoing ART from five centers. Five of them were excluded because pSS was diagnosed after pregnancy. Three patients were excluded for SS secondary to SLE. Finally, 24 successful cycles out of 51 ART cycles in 24 patients were analyzed. Clinical pregnancy rate was 47.1% (24/51). The mean age at conception was 34.3 ± 5.2 years. The mean body mass index (BMI) at pregnancy was 25.0 ± 3.7 kg/m2. The median (IQR) disease course was 12 (11.5, 24.3) months. Six patients (25.0%) were pluripara. Half of them (13/24, 54.2%) had past histories of adverse obstetric outcomes. Spontaneous abortion was the most common (10/24, 41.7%) (Table 1).

Table 1 Basic characteristics in patients with pSS and ART

Ten patients were taking prednisone prior to ART for the reasons of arthritis (n = 4), rash (n = 2), thrombocytopenia (n = 3), and leukopenia (n = 1). Seven patients continued to take prednisone during pregnancy. Cyclosporin A (CsA) was given to two patients with thrombocytopenia prior to ART, and one of them continued the therapy during pregnancy. The majority of patients with pSS undergoing ART (20/24, 83.3%) were taking hydroxychloroquine (HCQ) during pregnancy.

Manipulation of ART

Underlying causes for infertility in pSS are shown in Table 2. Primary infertility accounted for 25.0% (6/24), followed by recurrent spontaneous abortion (4/24, 16.7%), and obstruction of fallopian tubes (2/24, 8.3%).

Table 2 Causes for infertility

Baseline reproductive function evaluated at day 3 of menstrual cycle in patients with pSS prior to ART was evaluated by obstetricians. The median (IQR) level of follicle-stimulating hormone (FSH) was 7.2 (6.0, 9.4) IU/l. The median (IQR) level of luteinizing hormone (LH) was 4.6 (3.8, 6.7) IU/l. The median (IQR) level of estrogen was 43.4 (36.0, 52.4) pg/ml. The median (IQR) level of anti-Müllerian hormone (AMH) was 2.0 (1.0, 3.1) ng/ml.

OI/COS was performed in 20 (87.0%) pregnancies, including long protocol (8/24, 33.3%), mini-dose protocol (4/24, 16.7%), modified natural cycle (4/24, 16.7%), antagonist protocol (3/24, 12.5%), and ultralong protocol (1/24, 4.2%). IVF was performed in 22 (91.7%) pregnancies, and ICSI in 1 (4.2%). One patient (4.2%) received PGT due to parental thalassemia. Neither ovarian hyperstimulation syndrome (OHSS) nor thrombotic event was observed.

Maternal Outcomes

Twenty-two (91.7%) pregnancies ended in successful delivery. Cesarean section was conducted in 14 pregnancies (58.3%). Maternal APOs are shown in Table 3. Premature delivery was a complication with the highest incidence (11/24, 45.8%). The incidence of GDM ranked second (3/24, 12.5%). Two fetal losses (8.3%) occurred due to spontaneous abortion (Table 4).

Table 3 Maternal pregnancy outcomesTable 4 Causes for fetal lossCauses for Premature Delivery

Preterm birth was primarily attributed to twin gestation (4/11, 36.4%) and fetal distress (3/11, 27.3%) (Table 5). The average delivery time of premature delivery was 33.5 ± 2.6 weeks of gestation in ART, including five patients (45.5%) with early premature delivery and six patients (54.5%) with late premature delivery. The average birthweight in preterm infants was 2124.5 ± 646.2 g.

Table 5 Causes for premature deliveryFetal and Neonatal Outcomes

Twenty-seven live infants were born, including five pairs of twins. The live birth rate was 93.1% (27/29). The average delivery time was 36.1 ± 3.3 weeks of gestation. The average birth weight was 2434.4 ± 722.1 g. Fetal APOs are shown in Table 6. LBW infants accounted for 25.9% (7/27), including four VLBW (16.7%). Six LBW infants were born prematurely and three LBW infants were from twin gestation. No infant with either neonatal lupus or congenital heart block (CHB) was born.

Table 6 Fetal and neonatal pregnancy outcomesComparison Among pSS Patients Undergoing ART, Planned Pregnancy, and Healthy ControlsBasic Characteristics

The age of pregnancy (34.3 vs. 32.6 vs. 34.0 years, P = 0.09) was comparable among three groups, while pre-pregnant BMI (25.0 vs. 22.9 vs. 21.1 kg/m2, P < 0.001) increased in pSS with ART. The incidence of past history of adverse pregnancy in three groups was similar (54.2% vs. 40.0% vs. 36.5%, P = 0.29). Previous spontaneous abortion was the most common in pSS groups (41.7% in ART, 27.1% in natural pregnancy), compared with only 5.2% in healthy controls (P < 0.001).

Causes for Infertility

Nearly half of the patients suffered from primary infertility (25.0%) or recurrent spontaneous abortion (16.7%) in pSS. Obstruction of fallopian tubes (30.2%), primary infertility (19.8%), and male factors (19.8%) appeared to be the leading causes in healthy population.

Maternal Outcomes

Pre-eclampsia occurred in one (4.2%) pSS patient in ART, six (8.6%) pSS patients in planned pregnancy, and one (1.0%) healthy patient with ART (P = 0.04). One pSS patient (1.4%) in planned pregnancy developed eclampsia. The risk of GDM did not differ among the three groups (12.5% vs. 11.4% vs. 10.4%, P > 0.99). The rate of fetal loss was comparable (8.3% vs. 11.4% vs. 10.4%, P = 0.95). The Cesarean section rate remained high among the three groups (58.3% vs. 55.7% vs. 58.3%, P = 0.94). Patients with ART were more likely to deliver prematurely compared with planned pregnancy and healthy control (45.8% vs. 20.0% vs. 7.3%, P < 0.001). Placental abruption occurred in six (25.0%) and 16 (22.9%) patients from ART and natural pregnancy in pSS, respectively. No patient with ART had disease flare during pregnancy.

Causes for Premature Delivery

Premature delivery was mainly attributed to twin gestation in ART (4/11, 36.4%) and fetal distress in natural pregnancy (4/14, 28.6%) in pSS. The predominant cause for premature delivery in healthy people with ART was twin gestation (5/7, 71.4%).

Fetal and Neonatal Outcomes

In comparison with planned pregnancy and healthy controls, delivery time in ART was earlier (36.1 vs. 37.6 vs. 38.5 weeks, P < 0.001) and birthweight was lower (2434.4 vs. 2844.9 vs. 3072.1 g, P < 0.001). Apgar score at 1 min (9.7 vs. 9.6 vs. 10.0, P = 0.01) and 5 min (9.9 vs. 9.9 vs. 10.0, P = 0.09) were lower in pSS compared with healthy controls.

LBW was more frequent in patients with pSS and ART although no statistical significance was found (25.9% vs. 22.2% vs. 13.0%, P = 0.09). The incidence of fetal distress increased in infants from pSS mothers (14.8% vs. 12.9% vs. 0%, P = 0.002), while the incidence of FGR was comparable (3.7% vs. 6.5% vs. 3.3%, P = 0.64).

Neonatal complications including neonatal pathological jaundice (3.7% vs. 8.3% vs. 6.5%, P = 0.54) and neonatal respiratory distress syndrome (NRDS) (0% vs. 1.4% vs. 0%, P = 0.49) did not differ among the three groups.