The influence of reproductively significant autoantibodies determined in the follicular fluid on the quality of the obtained oocytes and embryos, as well as on the implantation rate in assisted reproductive technology cycles

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Abstract

BACKGROUND: According to reports, the efficiency of in vitro fertilization and intra cytoplasmic sperm injection protocols is decreased in patients positive for various autoantibodies, as opposed to autoantibody negative patients. However, there are contradictory data indicating no autoantibody effect on the outcome of infertility treatment using assisted reproductive technology.

AIM: The aim of this study was to evaluate the embryological outcome and clinical efficiency of infertility treatment in in vitro fertilization and intra cytoplasmic sperm injection protocols in women in the presence of reproductively significant autoantibodies.

MATERIALS AND METHODS: This prospective study enrolled 90 infertile patients undergoing assisted reproductive technology treatment. The follicular fluid obtained on the day of oocyte retrieval was evaluated for a wide autoantibody panel using commercial ELISA kits. The main group (n = 52) included women with autoantibody levels determined in the follicular fluid of more than three standard deviations from the mean values determined among all patients. The comparison group consisted of 38 women with autoantibody levels of less than three standard deviations from all subjects. The intergroup comparative analysis included clinical and anamnestic data, hormonal parameters, ovarian reserve, embryological data, and in vitro fertilization and intra cytoplasmic sperm injection efficiency.

RESULTS: Reliably lower ovarian reserve parameters (anti-Mullerian hormone levels 1.9 (1.4; 4.0) vs. 3.3 (2.2; 6.5) ng/ml; p = 0.005; number of antral follicles 8.5 (6.0; 12.0) vs. 11.0 (9.0; 17.0); p = 0.003) have been noted in the main group relatively to the comparison group. The autoantibodies to thyroid peroxidase and cardiolipin content in the follicular fluid has been shown to be negatively associated with the number of two-pronuclear zygotes, the presence of autoantibodies to aromatase correlating negatively with the fertilization rate. Furthermore, the follicular fluid levels of autoantibodies to thyroid peroxidase (≥105 IU/ml) and cardiolipin (≥5.1 IU/ml) are reliably associated with a higher frequency of a suboptimal response to previous controlled ovarian stimulation, a lower incidence of high quality embryos on days 3 and 4 of in vitro cultivation, a decreased number of top-quality blastocysts, and the clinical efficiency of in vitro fertilization and intra cytoplasmic sperm injection programs.

CONCLUSIONS: The presence of reproductively significant autoantibodies is an independent risk factor for reducing the total efficiency of assisted reproductive technology treatment.

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About the authors

Galina Kh. Safarian

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

Email: galasaf07@gmail.com
ORCID iD: 0000-0001-5988-323X
SPIN-code: 7096-3838
Scopus Author ID: 57215531925

MD

Russian Federation, Saint Petersburg

Lyailya Kh. Dzhemlikhanova

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott; Saint Petersburg State University

Email: dzhemlikhanova_l@mail.ru
ORCID iD: 0000-0001-6842-4430
SPIN-code: 1691-6559
Scopus Author ID: 56896086100
ResearcherId: J-3441-2013

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg; Saint Petersburg

Igor Yu. Kogan

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott; St. Petersburg State University

Email: ikogan@mail.ru
ORCID iD: 0000-0002-7351-6900
SPIN-code: 6572-6450
Scopus Author ID: 56895765600

MD, Dr. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences

Russian Federation, Saint Petersburg; Saint Petersburg

Dariko A. Niauri

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; St. Petersburg State University

Email: d.niauri@mail.ru
ORCID iD: 0000-0003-1556-248X
SPIN-code: 4384-9785
Scopus Author ID: 12806465200
ResearcherId: G-8224-2015

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg; 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
ResearcherId: D-3880-2018

MD, Dr. Sci. (Med.)

Russian Federation, Saint Petersburg

Inna O. Krikheli

St. Petersburg State University

Email: ikrikhely@gmail.com
ORCID iD: 0000-0002-5439-1727
SPIN-code: 7356-6189
Scopus Author ID: 57200795744
ResearcherId: J-8653-2018

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Ksenia V. Ob’edkova

St. Petersburg State University

Email: obedkova_ks@mail.ru
ORCID iD: 0000-0002-2056-7907
SPIN-code: 2709-2890
Scopus Author ID: 57201161145
ResearcherId: A-7258-2019

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Elena A. Lesik

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

Email: lesike@yandex.ru
ORCID iD: 0000-0003-1611-6318
SPIN-code: 6102-4690

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Evgenia M. Komarova

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

Email: evgmkomarova@gmail.com
ORCID iD: 0000-0002-9988-9879
SPIN-code: 1056-7821

, Cand. Sci. (Biol.)

Saint Petersburg

Alexander M. Gzgzyan

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; St. Petersburg State University

Author for correspondence.
Email: agzgzyan@gmail.com
ORCID iD: 0000-0003-3917-9493
SPIN-code: 6412-4801
ResearcherId: G-7814-2015

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg; Saint Petersburg

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Supplementary files

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2. Fig. 1. Comparative evaluation of serum anti-Mullerian hormone concentration in the study groups. * Mann–Whitney U-test used; group differences are significant at p < 0.05

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3. Fig. 2. Comparative analysis of antral follicle count in the study groups. * Mann–Whitney U-test used; group differences are significant at p < 0.05

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4. Fig. 3. Comparative analysis of suboptimal response frequency among patients investigated depending on the threshold serum and follicular fluid autoantibodies’ values estimated by logistic regression. АТ-ТРО — thyroid peroxidase autoantibodies; anti-CL — autoantibodies to cardiolipin; FF — follicular fluid. * Pearson’s χ2 test; ** Yates’ χ2 test; group differences are significant at p < 0.05

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5. Fig. 4. Depend of the number of two-pronuclear zygotes on follicular fluid thyroid peroxidase autoantibodies values in women of both group

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6. Fig. 5. Depend of the number of two-pronuclear zygotes on follicular fluid autoantibodies to cardiolipin values in women of both group

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7. Fig. 6. Depend of fertilization efficiency in relation to follicular fluid anti-aromatase antibody values estimated by multivariate linear regression analysis

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8. Fig. 7. Comparative analysis of high-quality embryos on the 3rd (a) and 4th (b) days of development in the setting of in vitro fertilization and intra cytoplasmic sperm injection depending on the threshold values of follicular fluid autoantibodies. АТ-ТРО — thyroid peroxidase autoantibodies; anti-CL — autoantibodies to cardiolipin; FF — follicular fluid. Fisher’s two-tailed exact test was used. * Two-tailed Fisher’s exact test was used; group differences are significant at p < 0,05

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