Preview

Obstetrics, Gynecology and Reproduction

Advanced search

ROLE OF COMBINED THERAPY IN THE TREATMENT OF PATIENTS WITH INFERTILITY AND REPRODUCTIVE FAILURES

https://doi.org/10.17749/2313-7347.2018.12.1.005-015

Full Text:

Abstract

Introduction. Inflammatory gynecological disease is among the major causes of recurrent implantation failures (RIF). In hysteroscopy, chronic endometritis (CE) is diagnosed in one of three women with reproductive dysfunction. Search for novel therapeutic strategies aimed at improving the endometrium condition to overcome the RIF, remains an important goal of reproductive medicine.

Aims of the study: 1) identify clinical markers of infertility and RIF; 2) characterize the structural and functional changes in the endometrium of women with infertility and RIF; 3) test the efficacy of the proposed combined therapy in correcting of «uterine factor» of infertility in women with previous in vitro fertilization (IVF) failures.

Materials and methods. This cohort retrospective study included 154 patients: Group 1 – 87 women with the tubal factor of infertility; Group 2 – 67 women with adenomyosis. The inclusion criteria: age < 45, ≥ 2 previous IVF failures, the absence of severe non-gynecological disease. After detailed clinical and laboratory examination, we initiated a series of measures for endometrial rehabilitation by using: non-steroid anti-inflammatory drugs (if indicated); tissue regeneration (physiotherapy); immune modulators; improvement of blood rheology; fibrinolytic medication (conjugated hyaluronidase «Longidase», Petrovax Pharm, Russia).

Results. In women with the tubal factor of infertility, CE was diagnosed significantly more often (р < 0.05) than in patients with adenomyosis; and in women with adenomyosis, the prevalent (compared to CE) diagnoses were endometrial hyperplasia, intrauterine synechiae and decreased uterine perfusion (р < 0.05). In CE, under-expression of estrogen and progesterone receptors of the endometrium was found in 56.5% cases – significantly more often (р < 0.05) than in patients with adenomyosis. Upon the completion of the proposed therapy, the endometrium thickness was significantly greater in patients with adenomyosis (7.6 ± 1.5 mm versus 11.1 ± 1.3 mm; р < 0.05); in 93.1% of the patients, the sex hormone receptors were restored; in 96.8% of these women, normal uterine perfusion was found. Clinical and morphological signs of CE disappeared in 50% of the treated patients. In this group, the pregnancy rate was 57.1%.

Conclusion. Morphologic and functional improvements of the endometrium increase the pregnancy rate in women with the «uterine factor» of infertility. We consider the administration of conjugated hyaluronidase «Longidase» a major factor of the proposed combined therapy. The drug is characterized by fibrinolytic and anti-inflammatory activities. This combined therapeutic approach is expected to contribute to the treatment of RIF.

About the Authors

E. V. Vartanyan
Clinic for Assisted Reproductive Technologies «Test-Tube Babies»; Peoples’ Friendship University of Russia
Russian Federation

Vartanyan Emma Vramovna – MD, Director of Clinic for ARTs «Test-Tube Babies», obstetrician-gynecologist, expert in reproduction medicine; Professor of the Department of Obstetrics, Gynecology and Reproductive Medicine, Faculty of Continuing Medical Education, Medical Institute of PFUR; President of SRS «Association of ART clinics».

2, ul. Shukinskaya, Moscow, 123182; 6, ul. Miklukho-Maklaya, Moscow, 117198, +7(495)9818580


E. A. Devyatova
Clinic for Assisted Reproductive Technologies «Test-Tube Babies»
Russian Federation

Devyatova Ekaterina Alexandrovna – PhD, ultrasound radiologist, obstetrician-gynecologist.

2, ul. Shukinskaya, Moscow, 123182, +7(903)6645417



K. A. Tsaturova
Clinic for Assisted Reproductive Technologies «Test-Tube Babies»
Russian Federation

Tsaturova Kristina Ashotovna – PhD, obstetrician-gynecologist, expert in reproduction medicine, chief physician.

2, ul. Shukinskaya, Moscow, 123182, +7(495)9818580



D. R. Aglyamova
Clinic for Assisted Reproductive Technologies «Test-Tube Babies»
Russian Federation

Aglyamova Dinara Raisovna – obstetrician-gynecologist, expert in reproduction medicine.

2, ul. Shukinskaya, Moscow, 123182, +7(495)9818580



References

1. Dondorp W., de Wert G. Innovative reproductive technologies: risks and responsibilities. Hum Reprod. 2011; 26 (7); 1604-8.

2. Williams Cynecology [Eds. B.L. Hoffman, J.O. Schorge, K.D. Bradshaw et al.]. 3rd ed. McGraw-Hill Education. 2016: 1270 p.

3. Polyzos N.P., Valachis A., Patavoukas A. et al. Publication bias in reproductive medicine: from the European Society of Human Reproduction and Embryology annual meeting to publication. Hum Reprod. 2011; 26 (6): 1371-6.

4. Park H.J., Kim Y. Sh., Yoon T.K. et al. Chronic endometritis and infertility. Clin Exp Reprod Med. 2016; 43 (4): 185-92.

5. Sukhikh G.T., Shurshalina A.V. Chronic endometritis [Hronicheskij endometrit]. Moskva: GEOTAR-Media. 2010: 64 s (in Russian).

6. McQueen D.B., Perfetto C.O., Hazard F.K. Pregnancy outcomes in women with chronic endometritis and recurrent pregnancy loss. Fertil Steril. 2015; 104 (4): 927-31.

7. Pelzer E.S. Microbial colonization of follicular fluid: alterations in cytokine expression and adverse assisted reproduction technologies outcomes. Hum Reprod. 2011; 26 (7): 1799-812.

8. Jones R.L., Hannan N.J., Kaituu T.J., Zhang J., Salamonsen L.A. Identification of chemokines important for leukocyte recruitment to the human endometrium at the times of embryo implantation and menstruation. J Clin Endocrinol Metab. 2004; 89: 6155-67.

9. Serebrennikova K.G., Bessmertnaya V.S., Samoilov M.V., Shulchina I.V., Khmelevskaya V.F. Modern approaches to assessing the state of the endometrium in preparation for extracorporeal fertilization and embryo transfer (IVF and PE) [Sovremennye podhody v ocenke sostoyaniya endometriya pri podgotovke k ekstrakorporal'nomu oplodotvoreniyu i perenosu embrionov (EKO i PE)]. II Regional'nyj nauchnyj forum «Mat' i ditya»: tezisy dokladov. Sochi. 2008: 209 (in Russian).

10. Kellat E.P., Shurshalina A.V., Korneeva E.I. The role of endometrium in the failure of realization of the reproductive function (literature review) [Rol' endometriya v neudachah realizacii reproduktivnoj funkcii (obzor literatury)]. Problemy reprodukcii. 2010; 2: 31-5 (in Russian).

11. Linde V.A., Tatarova N.A., Grishanina O.I. Immunological aspects of endometriosis (literature review) [Immunologicheskie aspekty endometriozov (obzor literatury)]. Problemy reprodukcii. 2008; 4: 74-7 (in Russian).

12. Balan V.Е., Zhuravel A.S. The possibilities of using drugs containing hyaluronic acid in gynecology [Vozmozhnosti primeneniya preparatov, soderzhashchih gialuronovuyu kislotu, v ginekologii]. Effektivnaya farmakoterapiya. 2014; 23: 50-5 (in Russian).

13. Vartanyan E.V. Overcoming repeated failures ART [Preodolenie povtornyh neudach VRT]. Avtoref. dis. dokt. med nauk. Moskva. 2012: 34 s (in Russian).

14. Gulmukhammedova D.Ch., Totchiev G.F., Toktar L.R. et al. Pathogenesis, diagnosis and treatment of chronic endometritis [Patogenez, diagnostika i lechenie hronicheskogo endometrita]. Vestnik RUDN. Seriya Medicina. 2011; 5: 261-7 (in Russian).

15. Rybalka A.N., Sulima A.N., Yakovchuk E.K., Dizha M.A. Chronic endometritis: ways to solve the problem (review of the literature) [Hronicheskij endometrit: puti resheniya problemy (obzor literatury)]. LIV-LV mezhdunarodnaya nauchno-prakticheskaya konferenciya «Sovremennaya medicina: aktual'nye voprosy». Novosibirsk: SibAK. 2016: 14-23 (in Russian).

16. Early pregnancy [Rannie sroki beremennosti (Pod red. V.E. Radzinskogo, A.A. Orazmuradova)]. Moskva: Status Praesens. 2009: 480 s (in Russian).

17. Unanyan A.L., Kossovich Yu.M. Chronic endometritis: etiopathogenesis, diagnosis, clinic and treatment. The role of antifibrotic therapy [Hronicheskij endometrit: etiopatogenez, diagnostika, klinika i lechenie. Rol' antifibroziruyushchej terapii]. Lechashchij vrach. 2012; 11: 35-40 (in Russian).

18. Kulakov V.I. Infertile marriage. Modern approaches to diagnosis and treatment [Besplodnyj brak. Sovremennye podhody k diagnostike i lecheniyu]. Moskva: GEOTAR-Media. 2006: 616 s (in Russian).

19. Mongiat M., Andreuzzi E., Tarticchio G. Extracellular Matrix, a Hard Player in Angiogenesis. Int J Mol Sci. 2016; 17 (1822). DOI: 10.3390/ijms17111822. URL: www.ncbi.nlm.nih.gov/pmc/articles/PMC5133823/pdf/ijms-17-01822.pdf. [Accessed: 22.12.2017].

20. Leone F.P.G., Timmerman D., Bourne T. et al. Terms, definitions and measurements to describe the sonographic features of the endometrium and intrauterine lesions: a consensus opinion from the International Endometrial Tumor Analysis (IETA) group. Ultrasound Obstet Gynecol. 2010; 35: 103-12. DOI: 10.1002/uog.7487.

21. Van den Bosch T., Dueholm M., Leone F.P.G. et al. Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group. Ultrasound Obstet Gynecol. 2015. DOI: 10.1002/uog.14806. URL: www.onlinelibrary.wiley.com/doi/10.1002/uog.14806/full. [Accessed: 22.12.2017].

22. Radzinsky V.Ye., Dimitrova V.I., Mayskova I.Yu. Non-developing pregnancy [Nerazvivayushchayasya beremennost']. Moskva: GEOTAR-Media. 2009: 196 s (in Russian).

23. Sidelnikova V.M. Infection as a risk factor for miscarriage [Infekciya kak faktor riska nevynashivaniya beremennosti]. Ginekologiya. 2008; 10 (5): 28-30 (in Russian).

24. Johnston-MacAnanny E.B., Hartnett J., Engmann L.L. et al. Chronic endometritis is a frequent finding in women with current implantation failure after in vitro fertilization. Fertil Steril. 2010; 93 (2): 437-41.

25. Amirova A.A., Nazarenko T.A., Mishieva N.G. Factors affecting the outcomes of IVF (literature review) [Faktory, vliyayushchie na iskhody EKO (obzor literatury)]. Problemy reprodukcii. 2010; 1: 34-7 (in Russian).

26. Boguslavskaya D.V., Lebovic D.I. Endometriosis and infertility (review of literature) [Endometrioz i besplodie (obzor literatury)]. Problemy reprodukcii. 2011; 2: 69-74 (in Russian).

27. Endometriosis: diagnosis, treatment and rehabilitation. Clinical recommendations [Endometrioz: diagnostika, lechenie i reabilitaciya. Klinicheskie rekomendacii]. Moskva. 2013: 86 s (in Russian).

28. Fertility-sparing surgery in malignant and benign conditions. The ESHRE Special Interest Group Reproductive Surgery. Munich, Germany. 2014: 150 р.

29. Petrov Yu.A. Hysteroscopic characteristics of endometrium in women with early reproductive losses [Gisteroskopicheskaya harakteristika endometriya zhenshchin s rannimi reproduktivnymi poteryami]. Vestnik RUDN. Seriya Medicina. 2011; 5: 243-7 (in Russian).

30. Aboubakr M.E., Aboul-Enein G.I. Endometrial receptivity. Middle East Fertility Society J. 2004; 9 (1): 10-24.

31. Smetnik A.A. Estrogen receptors and their functions (literature review) [Estrogenovye receptory i ih funkcii (obzor literatury)]. Problemy reprodukcii. 2011; 3: 11-5 (in Russian).

32. Recurrent Pregnancy Loss. Guideline of the European Society of Human Reproduction and Embryology. ESHRE Early Pregnancy Guidline Development Group. 2017: 154 p.

33. Lysenko O.V., Zanko S.N. Cytokines and sFas-ligand in hyperplastic processes and polyps of the endometrium) [Citokiny i sFas-ligand pri giperplasticheskih processah i polipah endometriya]. Problemy reprodukcii. 2010; 5: 46-8 (in Russian).


For citation:


Vartanyan E.V., Devyatova E.A., Tsaturova K.A., Aglyamova D.R. ROLE OF COMBINED THERAPY IN THE TREATMENT OF PATIENTS WITH INFERTILITY AND REPRODUCTIVE FAILURES. Obstetrics, Gynecology and Reproduction. 2018;12(1):5-15. (In Russ.) https://doi.org/10.17749/2313-7347.2018.12.1.005-015

Views: 165


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)