Morphological characteristics of the endometrium in the preconception period, chorion and placenta during pregnancy resulting from in vitro fertilization in patients with chronic endometritis (secondary analysis of the results of the TULIP-2 randomized controlled trial)

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Abstract

Background: Chronic endometritis (CE) is associated with unsuccessful attempts of in vitro fertilization (IVF) in 7.7–67.5% of patients.

Objective: To determine the characteristics of the morphological structure of the endometrium, chorion and placenta in patients with favourable and unfavourable pregnancy outcomes resulting from IVF with cryotransfer, after treatment of chronic endometritis in the preconception period using a complex of natural antimicrobial peptides and cytokines.

Materials and methods: A total of 600 patients with CE and infertility who underwent IVF (cryopreservation of one embryo) were selected from the electronic database. The analysis included the results of morphological examination of their endometrium, chorion and placenta after the treatment of CE in the preconception period. The patients of group I received the Superlymph drug, an antibiotic and a progestogen, patients of group II received an antibiotic and a progestogen, and then only a progestogen for up to 6 months in both groups). The morphological structure of the endometrium was assessed before and after treatment before conception, and the chorion/placenta after pregnancy.

Results: The average age of the patients was 36 (33–38) years, duration of infertility was 6.0 (4.5–7.0) and 5.5 (4.0–6.5) in groups I and II, respectively, p=0.06. The pregnancy rate as a result of cryotransfer was 57.0 versus 38.7%, respectively (RR=1.47; 95% CI: 1.24–1.75, p<0.001). Live birth rate was 45.3 and 20.7%, respectively (RR=2.19; 95% CI: 1.70–2.83, p<0.0001).

After treatment in the preconception period, the structure of the endometrium in patients in group I corresponded to the cycle phase in 85.3%, in group II – in 60.3%. After spontaneous miscarriage in the first trimester, more patients in group I than in group II had a complete gravidar transformation (RR=9.06, 95% CI: 2.35–35.0, p<0.001) with fewer signs of hematogenous infection in the chorion and its gestational immaturity. In both groups, the histological structure of the placenta after miscarriage at 120–216 weeks corresponded to the gestation period with the deposition of intercellular fibrinoid, ectasia and vascular fullness, and signs of infection. After preterm birth, the weight and thickness of the placenta were statistically significantly higher in patients in group I, however, the morphological structure differed only in a smaller number of syncytial kidneys and fibrosis of the basal plates, the remaining indicators in both groups showed that the placenta did not match the gestation period. In patients who had full-term birth, the placenta mass was comparable; as for the rest of the parameters, there was a statistically significant difference between patients of groups I and II with a decrease in the risk of defective structure in most indicators by 2 to 9 times in favour of group I. This difference determined a 2.7-fold lower risk of complications during pregnancy in patients of group I (RR=0.37, 95% CI: 0.27–0.52, p<0.001).

Conclusion: There are morphological signs of chorionic/placental inferiority in patients with CE and unsuccessful outcomes of pregnancy resulting from IVF, which determine the necessity of restoring the structure and function of the endometrium before conception. Morphological examination of the endometrium before IVF planning in patients who received a course of complex treatment, including Superlymph during preconception period, indicates a significant improvement in the structure of the endometrium compared with the control group (matching the day of the cycle, reduction of spiral artery sclerosis and periglandular fibrosis), which improves the results of IVF and pregnancy outcomes.

About the authors

Anton A. Sukhanov

Perinatal Medical Center; Tyumen State Medical University, Ministry of Health of Russia

Author for correspondence.
Email: such-anton@yandex.ru
ORCID iD: 0000-0001-9092-9136

PhD, Head of the Department of Family Planning and Reproduction, Tyumen Perinatal Center; Associate Professor, Department of Obstetrics and Gynecology, Tyumen State Medical University, Ministry of Health of Russia

Russian Federation, Tyumen; Tyumen

Galina B. Dikke

F.I. Inozemtsev Academy of Medical Education

Email: galadikke@yandex.ru
ORCID iD: 0000-0001-9524-8962

Dr. Med. Sci., Professor of the Department of Obstetrics and Gynecology with a Course of Reproductive Medicine

Russian Federation, St. Petersburg

Irina I. Kukarskaya

Perinatal Medical Center; Tyumen State Medical University, Ministry of Health of Russia

Email: kukarskay@mail.ru
ORCID iD: 0000-0002-8275-3553

Dr. Med. Sci., Professor of the Department of Obstetrics, Gynecology and Reanimatology with a Course of Clinical Laboratory Diagnostics, Tyumen State Medical University, Ministry of Health of Russia; Chief Specialist in Obstetrics and Gynecology, Department of Health of the Tyumen Region

Russian Federation, Tyumen; Tyumen

Anastasia V. Pesotskaya

Altai Regional Clinical Perinatal Center

Email: pesokpesotskaya@yandex.ru
ORCID iD: 0000-0002-4625-0916

Head of the Pathological Laboratory with the Department of Immunohistochemistry

Russian Federation, Barnaul

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2. Fig. 1. Histologic structure of the chorion after early miscarriage: group 1 - group 1 (patient A., gestational age 11 weeks. Signs of hematogenous infection), group 2 - group II (patient B., gestational age 9 weeks. Secondary exudative-necrotic deciduitis). Hematoxylin, eosin; eq. x20.

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3. Fig. 2. Results of histologic examination of the placenta after late miscarriage: 1 - group I (patient G., gestational age - 18 weeks. Focal exudative-necrotic deciduitis), 2 - group II (patient E., gestational age - 17 weeks. Basal productive deciduitis, focal productive villusitis). Hematoxylin, eosin; eq. *20

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4. Fig. 3. Results of histologic examination of the placenta after preterm labor: 1 - group I (patient N., gestational age - 32 weeks. Gestational immaturity of the placenta), 2 - group II (patient M., gestational age - 31 weeks. Gestational immaturity of the placenta). Hematoxylin, eosin; eq. x20.

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5. Fig. 4. Results of histologic examination of the placenta after term delivery: 1 - group I (patient K., gestational age - 40 weeks. Moderately expressed involutional-dystrophic changes and compensatory-adaptive reactions), 2 - Group II (patient L., gestational age 39-40 weeks. Ascending bacterial infection stage II). Hematoxylin, eosin; eq. x20.

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