The effectiveness of pregravidar preparation in women with infertility against the background of undifferentiated connective tissue dysplasia: a clinical case

• Olga V. Shestakova
• Faina K. Tetelyutina

Abstract

Infertility is an urgent problem among married couples. To solve this problem today, the most common method is in vitro fertilization. To increase the effectiveness of in vitro fertilization, an interdisciplinary approach is needed in order to thoroughly study the patient’s body. The most poorly studied, but common disease is undifferentiated connective tissue dysplasia (UCTD), namely the state of steroid hormone receptors in connective tissue dysplasia. Women with this pathology are characterized by infertility and complicated pregnancy and childbirth. One of the leading causes of infertility against the background of connective tissue dysplasia is a slowdown in the processes of connective tissue remodeling, a weakening of microcirculation, which in turn leads to a decrease in the trophism of the endometrial stroma and an increase in sclerosis processes in it, and, as a result, a decrease in endometrial receptivity, an imbalance of progesterone and estrogen receptors. The presented clinical case of a patient with infertility on the background of connective tissue dysplasia was the basis for discussing the optimal choice of management tactics for these women.

Conclusion. An integrated approach is needed to diagnose problems with conception and pregnancy in patients with UCTD. Taking into account the pathogenesis of infertility formation in UCTD, special attention in the treatment should be paid to the activation of steroid receptors. Treatment of luteal phase insufficiency, planning and management of pregnancy in this group of patients should be carried out while taking dydrogesterone. Dydrogesterone has a higher selectivity for progesterone receptors than micronized progesterone, which gives more chances for the onset, maintenance of pregnancy and live birth.

Keywords:infertility; in vitro fertilization; undifferentiated connective tissue dysplasia; dydrogesterone

REFERENCES

1. Adamyan L.V., Martirosyan Ya.O., Asaturova A.V. Etiopathogenesis of endometriosis-associated infertility (literature review). Problemy reproduktsii [Problems of Reproduction]. 2018; (2): 28–33. (in Russian)

2. Korsak V.S. A guide to assisted reproductive technologies for doctors and embryologists. Moscow: SIMK, 2015: 240 p. (in Russian)

3. Nazarenko T.A. Stimulation of ovarian function. 5th ed., revised and additional. Moscow: MEDpress-inform, 2015: 288 p. (in Russian)

4. Clinical recommendations of the Russian Scientific Medical Society of Physicians for the diagnosis, treatment and rehabilitation of patients with connective tissue dysplasia (first revision) approved at the XII National Congress of Physicians on November 22–24, 2017. Meditsinskiy vestnik Severnogo Kavkaza [Medical Bulletin of North Caucasus]. 2018; 13 (1.2): 137–209. (in Russian)

5. Kogan E.A., Nikolenko V.N., Zanozin A.S., Demura T.A. Syndrome of undifferentiated connective tissue dysplasia in combination with hereditary thrombophilia as a cause of primary female infertility. Meditsinskiy vestnik Severnogo Kavkaza [Medical Bulletin of North Caucasus]. 2016; 11 (2): 323–6. (in Russian)

6. Morozov D.A., Bogomolova N.V., Kulikova T.N., Deryugina L.A., Nikitina A.S. Cryptorchidism in the structure of undifferentiated forms of connective tissue dysplasia. Saratovskiy nauchno-meditsinskiy vestnik [Saratov Scientific Medical Bulletin]. 2004; 1 (4): 79–87. (in Russian)

7. Nechaeva G.I., Viktorova I.A. Connective tissue dysplasia: terminology, diagnosis, management tactics. Omsk: Tipografiya BLANKOM, 2007: 11–47. (in Russian)

8. Tvorogova T.M., Vorob’eva A.S. Undifferentiated connective tissue dysplasia from the standpoint of diselementosis in children and adolescents. RMZh [Russian Medical Journal]. 2012; (24): 1215–21. (in Russian)

9. Shestakova O.V., Tetelyutina F.K. Comparative assessment of the health status of couples with infertility against the background of undifferentiated connective tissue dysplasia. Problemy reproduktsii [Problems of Reproduction]. 2018; (4): 41–7. (in Russian)

10. Ades L.; CSANZ Cardiovascular Genetics Working Group. Guidelines for the diagnosis and management of Marfan syndrome. Heart Lung Circ. 2007; 16 (1): 28–30.

11. Kadurina T.I., Gorbunova V.N. Connective tissue dysplasia. Guide for doctors. Saint Petersburg: ELBI SPb, 2009: 704 p. (in Russian)

12. Kalaeva G.Yu., Zaytseva A.Kh., Khokhlova O.I., et al. Clinical and functional manifestations of undifferentiated connective tissue dysplasia in adolescents. Pediatriya [Pediatrics]. 2012; 91 (2): 135–9. (in Russian)

13. Demidov R.O., Lapshina S.A., et al. Connective tissue dysplasia: modern approaches to the clinic, diagnosis and treatment. Prakticheskaya meditsina [Practical Medicine]. 2015; (4): 37–41. (in Russian)

14. Arsent’ev V.G. Connective tissue dysplasia as a constitutional basis for multiple organ disorders in children: Autoabstract of Diss. Saint Petersburg, 2013: 40 p. (in Russian)

15. Genov O.A. Prevalence and some clinical and pathogenetic aspects of undifferentiated connective tissue dysplasia in adolescents: Autoabstract of Diss. Khabarovsk, 2011: 24 p. (in Russian)

16. Bravo J.F., Wolff C. Clinical study of hereditary disorders of connective tissues in a Chilean population. Joint hypermobility syndrome and vascular Ehlers-Danlos syndrome. Arthritis Rheum. 2006; 54 (2): 515–23.

17. Skal’naya M.G., Notova S.V. Macro- and microelements in the nutrition of modern man; ecological-physiological and social aspects. Moscow: ROMEM, 2004: 310 p. (in Russian)

18. Klemenov A.V., Tkacheva O.N., Vertkin A. L. Connective tissue dysplasia and pregnancy (review). Terapevticheskiy arkhiv [Therapeutic Archive]. 2004; 76 (11): 80–4. (in Russian)

19. Il’ina I.Yu., Dobrokhotova Yu.E., Yumina S.V. Hormonal status in women of the reproductive period with connective tissue dysplasia. Vestnik Rossiyskogo universiteta druzhby narodov [Bulletin of the Russian University of Peoples’ Friendship]. 2010; (2): 65–8. (in Russian)

20. Il’ina I.Yu. Influence of hormones on collagen metabolism in women with and without connective tissue dysplasia. Vestnik Rossiyskogo universiteta druzhby narodov [Bulletin of the Russian University of Peoples’ Friendship]. 2009; (5): 207–15. (in Russian)

21. Jacobsen B.M., Horwitz K.B. Progesterone receptors, their isoforms and progesterone regulated transcription. Mol Cell Endocrinol. 2012; 357 (1–2): 18–29. DOI: https://doi.org/10.1016/j.mce.2011.09.016

22. Mirza F.G., Patki A., Pexman-Fieth C. Dydrogesterone use in early pregnancy. Gynecol Endocrinol. 2016; 32 (2): 97–106. DOI: https://doi.org/10.3109/09513590.2015.1121982 PMID: 26800266.

23. Oehler M.K., Rees M.C., Bicknell R. Steroids and the endometrium. Curr Med Chem. 2000; 7 (5): 543–60.

24. Rajaram R.D., Brisken C. Paracrine signaling by progesterone. Mol Cell Endocrinol. 2012; 357 (1–2): 80–90. DOI: https://doi.org/10.1016/j.mce.2011.09.018

25. Rižner T.L., Brožič P., Doucette C., Turek-Etienne T., Muller-Vieira U., Sonneveld E., et al. Selectivity and potency of the retroprogesterone dydrogesterone in vitro. Steroids. 2011; 76 (6): 607–15. DOI: https://doi.org/10.1016/j.steroids.2011.02.043 PMID: 21376746.

26. Schindler A.E., Campagnoli C., Druckmann R., et al. Classification and pharmacology of progestins. Maturitas. 2008; 61: 171–80.

27. Colombo D., Fcrraboschi P., Prestileo P., Torna L. A comparative molecular modeling study of dydrogesterone with other progestational agents through theoretical calculations and nuclear magnetic resonance spectroscopy! Steroid Biochem Mol Biol. 2006; 98: 56–62.

28. Griesinger G., Tournaye H., Macklon N., Petraglia F., Arck P., Blockeel C., et al. Dydrogesterone: pharmacological profile and mechanism of action as luteal phase support in assisted reproduction. Reprod Biomed Online. 2019; 38 (2): 249–59. DOI: https://doi.org/10.1016/j.rbmo.2018.11.017 PMID: 30595525.

29. Tetruashvili N.K., Serov V.N. Gestagens in high-risk pregnancy. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training]. 2022; 10 (2): 31–8. DOI: https://doi.org/10.33029/2303-9698-2022-10-2-31-38 (in Russian)

30. James M.F.M. Magnesium in obstetrics. Best Pract Res Clin Obstet Gynaecol. 2010; 24 (3): 327–37.

31. Apolikhina I.A., Shneyderman M.G., Teterina T.A., Gorbunova E.A. Causes of miscarriage. Ginekologiya [Gynecology]. 2013; 15 (5): 60–5. (in Russian)

32. Miscarriage. Clinical guidelines ROAG, 2021. ID: 670. (in Russian)

33. Isthmic-cervical insufficiency. Clinical guidelines ROAG, 2021. ID: 671. (in Russian)

34. Normal pregnancy. Clinical guidelines ROAG, 2020. ID: 288. (in Russian)

35. Habitual miscarriage. Clinical guidelines ROAG, 2022. ID: 721. (in Russian)

36. Female infertility. Clinical guidelines ROAG. 2021 ID: 641. (in Russian)

37. ART: choice of strategy. Innovatsionnaya farmakoterapiya [Innovative Pharmacotherapy]. 2021; (3): 30–4. URL: https://www.innofarma.ru/index.php?id=111 (in Russian)

38. Griesinger G., Blockeel C., Kahler E., Pexman-Fieth C., Olofsson J.I., Driessen S., et al. Dydrogesterone as an oral alternative to vaginal progesterone for IVF luteal phase support: a systematic review and individual participant data meta-analysis. PLoS One. 2020; 15 (11): e0241044. DOI: https://doi.org/10.1371/journal.pone.0241044

39. Astrakhantseva M.M., Myasoutova A.I., Breusenko L.E., et al. Miscarriage. Treatment options. Voprosy ginekologii, akusherstva i perinatologii [Problems of Gynecology, Obstetrics and Perinatology]. 2021; 20 (2): 75–84. DOI: https://doi.org/10.20953/1726-1678-2021-2-75-84 (in Russian)

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