Evaluation of the effectiveness of cytotherapy in women with early pregnancy loss

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Abstract

Background: Cytotherapy, or alloimmunization, with partner lymphocytes is a method of active immunocorrection through artificial immunization with allogeneic paternal or donor leukocytes or their fragments before and in the early stages of pregnancy, as an effective method for correcting immunoregulation, which will increase the effectiveness of assisted reproductive technologies protocols and the number of successful pregnancies ending in live birth in couples with recurrent pregnancy loss.

Aim: The aim of this study was to evaluate the clinical and laboratory effectiveness of cytotherapy in married couples with a history of reproductive disorders.

Materials and methods: The study included 77 married couples with recurrent miscarriage, primary infertility, and repeated implantation failure during in vitro fertilization. Inclusion criteria were age 20–44 years, 2 implantation failures during in vitro fertilization and more and/or 2 spontaneous abortions before 20 weeks of gestation and more, normal karyotypes of the abortus and partners, HLA (human leukocyte antigen, major histocompatibility complex) class II gene typing at three loci (DQA1, DQB1, DRB1) in the married couple. All women received cytotherapy as monotherapy before a planned pregnancy. To study the immune status, the patients’ blood was examined and the natural killer (NK) cell (CD3CD16+CD56+) and natural T-killer (NKT) cell (CD3+CD16+CD56+) counts, as well as NK cell activity, were determined by spontaneous or activated expression of CD107a.

Results: Of the 77 women included in the study, 32 individuals did not have 12 months to register their pregnancy, therefore, of the remaining 48 married couples, 32 (66.7%) ones had pregnancy registered within 12 months after immunization. Among patients with recurrent miscarriage, pregnancy occurred in 87.0% of cases, in which in 45.2% of cases it ended in the birth of a healthy full-term newborn, and in 29% of cases, pregnancy is currently developing. Among patients with primary infertility and repeated implantation failure during in vitro fertilization, pregnancy occurred in 35.3% of cases. When comparing the functional activities of NK cells in peripheral blood before and two weeks after the second cytotherapy, we found a decrease in the total NK cell count by 5.1% (p = 0.015).

Conclusions: Cytotherapy is an effective therapy in patients with recurrent early miscarriage and leads to pregnancy in 87% of cases and its prolongation after 13 weeks in 74% of cases. The effect of the procedure is justified by its immunoregulatory functions, which is manifested by a decrease in the total NK cell count.

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About the authors

Margarita O. Shengeliia

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Author for correspondence.
Email: bakleicheva@gmail.com
ORCID iD: 0000-0002-0103-8583
SPIN-code: 7831-2698

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Olesya N. Bespalova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953
SPIN-code: 4732-8089

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

Tatiana S. Zhernakova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: tatazhernakova@gmail.com
ORCID iD: 0000-0002-5131-4363
SPIN-code: 3913-7697

MD

Russian Federation, Saint Petersburg

Ekaterina A. Kornyushina

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: hapacheva@yandex.ru
ORCID iD: 0009-0003-5918-2697
SPIN-code: 5844-1975

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Olga V. Pachuliia

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: for.olga.kosyakova@gmail.com
ORCID iD: 0000-0003-4116-0222
SPIN-code: 1204-3160
Scopus Author ID: 57299197900

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Vyacheslav A. Semenov

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: semenov.v.a@gmail.com
ORCID iD: 0009-0001-1777-9650
Russian Federation, Saint Petersburg

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Distribution of the matches according to the HLA class II system among married couples with reproductive disorders

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3. Fig. 2. Distribution of the most frequent matches in alleles of the three HLA class II loci (DQA1, DQB1, DRB1) in married couples with reproductive disorders

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4. Fig. 3. Efficacy of cytotherapy based on pregnancy onset

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5. Fig. 4. Therapy outcomes in the examined women

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6. Fig. 5. Natural killer (NK) and natural T-killer (NKT) cell functional activity dynamics in peripheral blood before cytotherapy and two weeks after re-immunization. Dots denote “outliers” from the total statistical analysis group outside the 95% confidence interval

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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от 15.07.2002 г.