Ways to improve in vitro fertilization outcomes in patients with polycystic ovary syndrome phenotypes A and D (INO-1)
Krasnopolskaya K.V., Zarochentseva N.V., Orazov M.R., Burumkulova F.F., Levin V.A., Isakova K.M., Balabanova K.Sh., Garina A.O.
Objective: To study the effect of the combination of myoinositol (MI) and α-lactalbumin (α-LA) on the quality of oocytes and embryos and to evaluate the effectiveness of in vitro fertilization (IVF) treatment in patients with polycystic ovary syndrome (PCOS) taking into account the presence of insulin resistance and polymorphic variants of the follicle-stimulating hormone (FSH) receptor gene.
Materials and methods: An observational comparative single-center INO-1 study enrolled 224 patients with infertility and PCOS (phenotypes A and D) who were screened for insulin resistance and FSH receptor gene polymorphisms (Asn680Ser). The patients were randomly divided into four groups depending on the presence or absence of insulin resistance and polymorphic variants of the FSH receptor gene: group 1 (n=52) had FSH receptor gene polymorphism (+), insulin resistance (-), group 2 (n=55) had FSH receptor gene polymorphism (-), insulin resistance (+), group 3 (n=59) had FSH receptor gene polymorphism (+), insulin resistance (+), group 4 (n=58) had FSH receptor gene polymorphism (-), insulin resistance (-). Depending on the type of therapy, the patients in each group were divided into two subgroups. The patients of the 1st subgroup received a combination of MI 600 mg+α-LA+folic acid 200 mcg (Inofert Forte, ITALFARMACO, Italy) one capsule twice a day, orally, for a course duration of 3 months before starting the IVF program. The patients of the 2nd subgroup received folic acid 400 mcg per day routinely, orally, for a course duration of 3 months before starting the IVF program. The quality of oocytes and embryos and the pregnancy rate per embryo transfer in the IVF programs after preconception supplementation with MI+α-LA combination were evaluated.
Results: The rate of mature oocyte retrieval was significantly higher in patients of subgroup 1 with insulin resistance (groups 2 and 3) who received MI+α-LA supplementation compared to patients of subgroup 2 who received folic acid supplementation routinely. This rate was 80.8% versus 51.7% (p=0.045) in group 2 and 64.5% versus 35.7% (p=0.027) in group 3. The rate of obtaining good quality embryos was significantly higher in patients of subgroup 1 in groups 2 and 3, namely 65.4 % versus 37.9 % (p=0.042) in group 2 and 54.8 % versus 28.6 % (p=0.041) in group 3. Comparable results were obtained when the pregnancy rate per embryo transfer in IVF programs was assessed in those insulin-resistant patients who were administered the MI+α-LA combination. The outcome of IVF programs in group 2 was 53.8% versus 27.6% (p=0.047) and the outcome in group 3 was 41.9% versus 17.9% (p=0.045).
Conclusion: The administration of the MI+α-LA combination (Inofert Forte, ITALFARMACO, Italy) to patients diagnosed with PCOS and insulin resistance before the IVF treatment is advisable, as it helps to correct insulin resistance and increase ovarian sensitivity to gonadotropins. This results in obtaining mature oocytes and embryos of good quality and increases the pregnancy rate.
Authors’ contributions: Krasnopolskaya K.V., Zarochentseva N.V. – developing the concept and design of the study; Isakova K.M., Balabanova K.Sh. – collecting and processing the material; Levin V.A., Garina A.O. – statistical processing of the data; Levin V.A., Isakova K.M. – writing the text; Burumkulova F.F., Orazov M.R. – editing the article.
Conflicts of interest: Authors declare lack of the possible conflicts of interest.
Funding: The study was conducted without sponsorship.
Ethical Approval: The study was approved by the Ethical Review Board of the Academician V.I. Krasnopolsky Moscow Regional Research Institute of Obstetrics and Gynecology.
Patient Consent for Publication: The patients who participated in the study signed an informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Krasnopolskaya K.V., Zarochentseva N.V., Orazov M.R., Burumkulova F.F., Levin V.A., Isakova K.M., Balabanova K.Sh., Garina A.O. Ways to improve in vitro fertilization outcomes in patients with polycystic ovary syndrome phenotypes A and D (INO-1).
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (2): 100-109 (in Russian)
https://dx.doi.org/10.18565/aig.2025.34
Keywords
polycystic ovary syndrome (PCOS)
infertility
oligomenorrhea
FSH receptor
insulin resistance
myoinositol (MI)
alpha-lactalbumin (α-LA)
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Received 14.02.2025
Accepted 20.02.2025
About the Authors
Kseniya V. Krasnopolskaya, Dr. Med. Sci., Professor, Corresponding Member of the RAS, Head of the Department of Reproductology, Academician V.I. KrasnopolskyMoscow Regional Scientific Research Institute of Obstetrics and Gynecology,
101000, Russia, Moscow, Pokrovka str., 22A, https://orcid.org/0000-0002-1275-9220
Nina V. Zarochentseva, Dr. Med. Sci., Professor of the Russian Academy of Sciences, Deputy Director for Research, Academician V.I. Krasnopolsky Moscow Regional
Scientific Research Institute of Obstetrics and Gynecology,
101000, Russia, Moscow, Pokrovka str., 22A, https://orcid.org/0000-0001-6155-788X
Mekan R. Orazov, Professor, Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology with a Course of Perinatology of the Medical Institute,
Patrice Lumumba Peoples’ Friendship University of Russia, 117198, Russia, Moscow, Miklukho-Maklaya str., 6, https://orcid.org/0000-0002-1767-5536
Fatima F. Burumkulova, Dr. Med. Sci., Professor, Senior Researcher, Academician V.I. Krasnopolsky Moscow Regional Scientific Research Institute of Obstetrics and Gynecology, 101000, Russia, Moscow, Pokrovka str., 22A, https://orcid.org/0000-0001-9943-0964
Vitaly A. Levin, endocrinologist, specialist in the field of organization of health and public health, Ornament Health AG, (Lucerne, Switzerland),
https://orcid.org/0009-0000-8758-0842
Kamila M. Isakova, PhD, obstetrician-gynecologist, reproductologist at the Department of Reproductology, Academician V.I. Krasnopolsky Moscow Regional Scientific Research Institute of Obstetrics and Gynecology, 101000, Russia, Moscow, Pokrovka str., 22A, https://orcid.org/0000-0001-6194-1654
Anastasiia O. Garina, obstetrician-gynecologist, PhD student at the Department of Reproductology, Academician V.I. Krasnopolsky Moscow Regional Scientific Research Institute of Obstetrics and Gynecology, 101000, Russia, Moscow, Pokrovka str., 22A; Teaching Assistant at the Department of Biomedical Technologies-1, Bauman
Moscow State Technical University, 105005, Russia, Moscow, 2nd Baumanskaya str., 5-1, +7(495)980-40-28, garinaa@inbox.ru, https://orcid.org/0000-0002-2313-746X
Kristina Sh. Balabanova, obstetrician-gynecologist, PhD student at the Department of Reproductology, Academician V.I. Krasnopolsky Moscow Regional Scientific
Research Institute of Obstetrics and Gynecology, 101000, Russia, Moscow, Pokrovka str., 22A, https://orcid.org/0000-0002-8581-9159
Corresponding author: Anastasiia O. Garina, garinaa@inbox.ru
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