DOI: https://doi.org/10.18370/2309-4117.2020.54.72-78

Micronized progesteron in complex pregravid preparation and pregnancy management in women with recurrent pregnancy loss on the background of chronic endometritis

С. І. Жук, С. Б. Чечуга, О. А. Ночвіна

Abstract


Purpose of the study: to determine the effectiveness of micronized progesterone with antibacterial therapy in the complex of pregravid training and during pregnancy in women with recurrent pregnancy loss on the background of chronic endometritis.

Materials and methods. It was assessed the course of pregnancy and childbirth on clinical and instrumental grounds with a prospective analysis of reproductive losses in women with recurrent miscarriage and chronic endometritis. 45 pregnant women with recurrent miscarriage on the background of chronic endometritis formed the main group and were prospectively examined. Main group were divided into subgroups: I subgroup – 24 patients who were included in the study at the stage of perconception training; subgroup II – 21 patients who were included in the study with a diagnosed pregnancy for up to 12 weeks. The control group consisted of 32 pregnant women with a normal course of previous pregnancies without a history of reproductive loss.

Results. Patients with recurrent miscarriage and chronic endometritis who received a complex of preconception training with support of the luteal phase with micronized progesterone showed a statistically significantly lower percentage of clinical symptoms of threatened abortion, with no significant difference in control group. Thus, only 2 (8.3%) patients lost pregnancy in the I subgroup who received the proposed preconception therapy, and 6 (28,5%) women lost pregnancy in the II subgroup who started taking micronized progesterone only from the moment of pregnancy diagnosed.

Conclusions. Obtained results prove the effectiveness of the micronized progesterone (Utrogestan®) at the stage of pre-pregnancy training in women with recurrent pregnancy loss and chronic endometritis, as evidenced by the percentage of reproductive losses. The universality of routes of administration for micronized progesterone and possibility of its use throughout pregnancy contributes to individualize of treatment regimens

Keywords


recurrent pregnancy loss; chronic endometritis; micronized progesterone; Utrogestan®; pregravid preparation

References


Ishchenko, L.S. Clinical and morphological aspects and ways to optimize the therapy of chronic endometritis. Thesis abstract for PhD degree. Moscow (2007): 23 p.

Serebrennikova, K.G., Lapshikhin, A.A., Kuznetsova, E.P., et al. “Chronic endometritis. Peculiarities of preparation for ART programs.” Reproductive technologies today and tomorrow. Materials of the XXI International Conference of the Russian Association for Human Reproduction. Sankt Petersburg (2011).

Sidelnikova, V.M. Preparation and management of pregnancy in women with recurrent miscarriage: methodological guidelines and clinical protocols. Moscow. MEDpress-inform (2011): 224 p.

Sidorova, I.S., Makarov, I.O., Unanyan, A.L. “Pathogenesis and pathogenetically justified therapy of chronic endometritis (clinical lecture).” Obstetrics, gynecology and reproduction 3 (2010): 21–4.

Sukhikh, G.T., Shurshalina, A.V. Chronic endometritis: Manual. Moscow. GEOTAR-Media (2010): 64 p.

Sheshukova, N.A., Makarov, I.O., Ovsyannikova, T.V. “Endometrial hyperplastic processes: features of proliferative activity in combination with chronic endometritis.” Obstetrics, gynecology and reproduction 3 (2011): 10–5.

Tolibova, G.K., Tral, T.G., Kleshchev, M.A., et al. “Endometrial Dysfunction: Algorithm for Histological and Immunohistochemical Research.” Journal of Obstetrics and Women's Diseases 4 (2015).

Instructions for medical use of the drug Utrogestan®.

Zhuk, S.I., Kondratiuk, V.K., Dziuba, G.A. Ethical code of a doctor who prescribes gestagens in obstetric and gynecological practice. Evidence base. Methodical recommendations. P.L. Shupik NMAPE; Department of Obstetrics, Gynecology and Fetal Medicine. Kyiv (2019): 23 p.

Reznikov, O.G., Zanko, S.N. “Utrozhestan is a progesterone with proven safety for mother and fetus.” Health of Ukraine. Thematic issue “Obstetrics” (2017).

Di Paola, R., Garzon, S., Giuliani, S., et al. “Are we choosing the correct FSH starting dose during controlled ovarian stimulation for intrauterine insemination cycles? Potential application of a nomogram based on woman's age and markers of ovarian reserve.” Arch Gynecol Obstet 298.5 (2018): 1029–35.

Vitagliano, A., Noventa, M., Saccone, G., et al. “Endometrial scratch injury before intrauterine insemination: is it time to re-evaluate its value? Evidence from a systematic review and meta-analysis of randomized controlled trials.” Fertil Steril 109.1 (2018): 84–96. e4.

Vitagliano, A., Saccardi, C., Noventa, M., et al. “Does endometrial scratching really improve intrauterine insemination outcome? Injury timing can make a huge difference.” J Gynecol Obstet Hum Reprod 47.1 (2018): 33–4.

Kitaya, K., Matsubayashi, H., Yamaguchi, K., et al. “Chronic endometritis: potential cause of infertility and obstetric and neonatal complications.” Am J Reprod Immunol 75.1 (2016): 13–22.

Michels, T.C. “Chronic endometritis.” Am Fam Physician 52.1 (1995): 217–22.

Coomarasamy, A., et al. “A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.” N Engl J Med 373 (2015): 2141–8.

Coomarasamy, A., et al. “A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy.” N Engl J Med 380 (2019): 1815–24.

Hirst, J.J., et al. “Neuroactive steroids in pregnancy: key regulatory and protective roles in the foetal brain.” J Ster Biochem (2014).

Norman, J. “Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial.” Lancet 387.10033 (2016): 2106–16.

Hassan, S.S., Romero, R., Vidyadhari, D., et al. “Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, placebo-controlled trial.” Ultrasound Obstet Gynec 38 (2011): 18–31.

Cetingoz, E., Cam, C., Sakali, M., et al. “Progesterone effect on preterm birth in high-risk pregnancies: a randomized placebo-controlled trial.” Arch Gynecol Obstet 283 (2011): 423–9.

Iams, J.D. “Prevention of Preterm Birth.” N Engl J Med 370 (2014): 254–61.

Rode, L., Kein, K., Nicolaides, K., et al. “Prevention of preterm delivery in twin gestations (PREDICT): a multicenter, randomized, placebo-controlled trial on the effect of vaginal micronized progesterone.” Ultrasound Obstet Gynecol 38 (2011): 272–80.

Romero, R., Nicolaides, K., Conde-Agudelo, A., et al. “Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: A systematic review and meta-analysis of individual patient data.” American Journal of Obstetrics and Gynecology 206.2 (2012): 124.e1–124.e19. DOI: 10.1016/j.ajog.2011.12.003

Di Renzo, G.C., et al. “Preterm labor and Birth Management: Recommendations from the European Association of Fetal Medicine.” The Journal of Maternal-Fetal & Neonatal Medicine 30.17 (2017): 2011–30. DOI: 10.1080/14767058.2017.1323860

Dodd, J.M., Jones, L., Flenady, V., et al. “Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth.” Cochrane Database Syst Rev 7 (2013): CD004947.


GOST Style Citations


1.      Ищенко, Л.С. Клинико-морфологические аспекты и пути оптимизации терапии хронического эндометрита : автореф. дисс. … канд. мед. наук. / Л.С. Ищенко. – М., 2007. – 23 с.

2.      Серебренникова, К.Г. Хронический эндометрит. Особенности подготовки к программам ВРТ / К.Г. Серебренникова, А.А. Лапшихин, Е.П. Кузнецова и др. // Репродуктивные технологии сегодня и завтра. Материалы XXI международной конференции Российской ассоциации репродукции человека. – СПб, 2011. – С. 65–67.

3.      Сидельникова, В.М. Подготовка и ведение беременности у женщин с привычным невынашиванием: методические пособия и клинические протоколы / В.М. Сидельникова. – М.: МЕДпресс-информ, 2011. – 224 с.

4.      Сидорова, И.С. Патогенез и патогенетически обоснованная терапия хронического эндометрита (клиническая лекция) / И.С. Сидорова, И.О. Макаров, А.Л. Унанян // Акушерство, гинекология и репродукция. – 2010. – № 3. – С. 21–24.

5.      Сухих, Г.Т. Хронический эндометрит: Руководство / Г.Т. Сухих, А.В. Шуршалина. – М.: ГЭОТАР-Медиа, 2010. – 64 с.

6.      Шешукова, Н.А. Гиперпластические процессы эндометрия: особенности пролиферативной активности при сочетании с хроническим эндометритом / Н.А. Шешукова, И.О. Макаров, Т.В. Овсянникова // Акушерство, гинекология и репродукция. – 2011. – № 3. – С. 10–15.

7.      Толибова, Г.Х. Эндометриальная дисфункция: Алгоритм гистологического и иммуногистохимического исследования / Г.Х. Толибова, Т.Г. Траль, М.А. Клещев и др. // Журнал акушерства и женских болезней. – 2015. – №4.

8.      Інструкція для медичного застосування препарату Утрожестан®.

9.      Жук, С.І. Етичний кодекс лікаря, який призначає гестагени в акушерсько-гінекологічній практиці. Доказова база. Методичні рекомендації / С.І. Жук, В.К. Кондратюк, Г.А. Дзюба; НМАПО ім. П.Л. Шупика. Кафедра акушерства, гінекології та медицини плода. – Київ, 2019. – 23 c.

10.    Резников, О.Г. Утрожестан – прогестерон з доведеною безпекою для матері і плода / О.Г. Резников, С.Н. Занько // Здоров’я України. Тематичний номер «Акушерство». – 2017.

11.    Di Paola, R., Garzon, S., Giuliani, S., et al. “Are we choosing the correct FSH starting dose during controlled ovarian stimulation for intrauterine insemination cycles? Potential application of a nomogram based on woman's age and markers of ovarian reserve.” Arch Gynecol Obstet 298.5 (2018): 1029–35.

12.    Vitagliano, A., Noventa, M., Saccone, G., et al. “Endometrial scratch injury before intrauterine insemination: is it time to re-evaluate its value? Evidence from a systematic review and meta-analysis of randomized controlled trials.” Fertil Steril 109.1 (2018): 84–96. e4.

13.    Vitagliano, A., Saccardi, C., Noventa, M., et al. “Does endometrial scratching really improve intrauterine insemination outcome? Injury timing can make a huge difference.” J Gynecol Obstet Hum Reprod 47.1 (2018): 33–4.

14.    Kitaya, K., Matsubayashi, H., Yamaguchi, K., et al. “Chronic endometritis: potential cause of infertility and obstetric and neonatal complications.” Am J Reprod Immunol 75.1 (2016): 13–22.

15.    Michels, T.C. “Chronic endometritis.” Am Fam Physician 52.1 (1995): 217–22.

16.    Coomarasamy, A., et al. “A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.” N Engl J Med 373 (2015): 2141–8.

17.    Coomarasamy, A., et al. “A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy.” N Engl J Med 380 (2019): 1815–24.

18.    Hirst, J.J., et al. “Neuroactive steroids in pregnancy: key regulatory and protective roles in the foetal brain.” J Ster Biochem (2014).

19.    Norman, J. “Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial.” Lancet 387.10033 (2016): 2106–16.

20.    Hassan, S.S., Romero, R., Vidyadhari, D., et al. “Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, placebo-controlled trial.” Ultrasound Obstet Gynec 38 (2011): 18–31.

21.    Cetingoz, E., Cam, C., Sakali, M., et al. “Progesterone effect on preterm birth in high-risk pregnancies: a randomized placebo-controlled trial.” Arch Gynecol Obstet 283 (2011): 423–9.

22.    Iams, J.D. “Prevention of Preterm Birth.” N Engl J Med 370 (2014): 254–61.

23.    Rode, L., Kein, K., Nicolaides, K., et al. “Prevention of preterm delivery in twin gestations (PREDICT): a multicenter, randomized, placebo-controlled trial on the effect of vaginal micronized progesterone.” Ultrasound Obstet Gynecol 38 (2011): 272–80.

24.    Romero, R., Nicolaides, K., Conde-Agudelo, A., et al. “Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: A systematic review and meta-analysis of individual patient data.” American Journal of Obstetrics and Gynecology 206.2 (2012): 124.e1–124.e19. DOI: 10.1016/j.ajog.2011.12.003

25.    Di Renzo, G.C., et al. “Preterm labor and Birth Management: Recommendations from the European Association of Fetal Medicine.” The Journal of Maternal-Fetal & Neonatal Medicine 30.17 (2017): 2011–30. DOI: 10.1080/14767058.2017.1323860

26.    Dodd, J.M., Jones, L., Flenady, V., et al. “Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth.” Cochrane Database Syst Rev 7 (2013): CD004947.





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

ISSN 2411-1295 (Online), ISSN 2309-4117 (Print)