The transcriptional profile of cumulus cells in women with diminished ovarian reserve in ovarian stimulation protocols in different phases of the menstrual cycle in in vitro fertilization programs
Objective. To explore the possibility of using the transcriptional profile in the cumulus cells to predict embryo quality in women with diminished ovarian reserve in the superovulation protocols in the follicular and luteal phases of the menstrual cycle.Bogatyreva Kh.A., Mishieva N.G., Burmenskaya O.V., Trofimov D.Yu., Martazanova B.A., Lapina V.S., Korolkova A.I., Martynova M.V., Abubakirov A.N.
Materials and methods. 160 cumulus cell samples from 40 patients with diminished ovarian reserve, who underwent an in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) program, were analyzed during this investigation. The retrieved oocyte-cumulus complexes were divided into 2 groups according to the treatment protocol phase. Group 1 (17 women; 70 samples) included oocytes obtained by IVF/ICSI procedures in the follicular phase of the cycle; Group 2 (23 women; 90 samples) comprised oocytes retrieved via IVF/ICSI during the luteal phase of the cycle. To identify the relationship between the expression levels of mRNA genes and the indicators of embryo quality in women with reduced ovarian reserve in the IVF/ICSI programs, the obtained cumulus cells were divided into three classes based on the quality of embryos according to the morphology assessment criteria: 1) good-quality embryos (n = 42); 2) satisfactory-quality embryos (n = 43); 3) poor-quality embryos (n = 17). A real-time RT-PCR assay was used to estimate cumulus cell mRNA expression for 10 genes: HAS2, PTGS2, GREM1, VCAN, ITPKA, ALCAM (CD166), SDC4, CALM2, SPSB, and TP53I3.
Results. Analysis of embryological indicators revealed no statistically significant differences. The mean number of oocytes retrieved on the day of transvaginal puncture was 3.6±1.9 and 4.2±2.0 in the follicular and luteal phase stimulation groups, respectively (p> 0.05). The number of blastocysts was 1.6±1.4 and 1.9±1.8, respectively (p > 0.05).
The cumulus cells of good-quality embryos displayed an increase in the mRNA expression levels for the HAS2, VCAN, and PTGS2 genes by 1.8, 2.0, and 2.9 times, respectively; and a decrease in that for the ITPKA gene by 1.9 times (p < 0.05). The logistic regression model was proposed to predict embryo quality in women with diminished ovarian reserve, which took into account mRNA expression levels for the VCAN, HAS2, and PTGS2 genes (the sensitivity and specificity of the technique were 90.5 and 70.6%, respectively). The mRNA expression level for the VCAN gene is the most important marker of embryo quality according to the morphology assessment criteria in the IVF/ICSI program. There was a statistically significant increase in the cumulus cell mRNA expression levels for the VCAN, SDC4, and TP53I3 genes in Study Group 2 (p = 0.003, p = 0.005, and
p < 0.001, respectively).
Conclusion. The mRNA expression levels for the VCAN, HAS2, and PTGS2 genes may be used as predictors for the good quality of developing embryos in women with diminished ovarian reserve. Superovulation induction during the luteal phase of the menstrual cycle has no negative impact on the developmental potential of oocytes and the quality of obtained embryos.
Keywords
infertility
ovarian stimulation
luteal phase
cumulus cells
mRNA gene expression
in vitro fertilization
Supplementary Materials
- Table 1. Clinical and anamnestic and embryological characteristics of patients included in the study
- Table 2. Level of mRNA expression of cumulus cells genes as a function of the phase of the IVF protocol
- Table 3. Level of mRNA expression of cumulus cells genes depending on embryo quality
- Table 4. The distribution of samples in the predicted embryo quality groups in accordance with the proposed statistical model
- Fig . 1. ROC-curves of the predictors of embryo quality
- Fig . 2. Distribution of values of the logarithmic regression function in research groups
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Received 15.05.2017
Accepted 23.06.2017
About the Authors
Bogatyreva Kh.A., postgraduate of 1st gynecology department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.117997, Russia, Mosсow, Ac. Oparina str. 4. Теl.: +79266085182. Е-mail: bogatyreva-khava@bk.ru
Mishieva N.G., PhD, MD, Senior researcher of 11st gynecology department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Mosсow, Ac. Oparina str. 4. Теl.: +74954382622. E-mail: nondoc555@mail.ru
Burmenskaya O.V., PhD., D.Sc., Senior Researsher of molecular-genetics Department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Mosсow, Ac. Oparina str. 4. Теl.: +74954381341. E-mail: o_bourmenskaya@oparina4.ru
Trofimov D.Yu., PhD, D.Sc., professor, Head of molecular-genetics Department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Mosсow, Ac. Oparina str. 4. Теl.: +74954381341. Е-mail: d_trofimov@oparina4.ru
Martazanova B.A., PhD, Junior Researcher of 1st gynecology department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Mosсow, Ac. Oparina str. 4. Теl.: +79671238824. Е-mail: bellamart88@mail.ru
Lapina V.S., postgraduate of 1st gynecology department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Mosсow, Ac. Oparina str. 4. Теl.: +79099202305. Е-mail: tifaniwow@gmail.com
Korolkova A.I., graduate student of 1-st gynecology department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Mosсow, Ac. Oparina str. 4. Теl.: +79153220879. E-mail: zaikinaai@icloud.com
Martynova M.V., PhD, doctor of 1-st gynecology department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Mosсow, Ac. Oparina str. 4. Теl.: +79167099373. Е-mail: martinova_m@bk.ru
Abubakirov A.N., PhD, Head of 1st gynecology department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Mosсow, Ac. Oparina str. 4. Теl.: +74954382622. Е-mail: nondoc555@mail.ru
For citations: Bogatyreva Kh.A., Mishieva N.G., Burmenskaya O.V., Trofimov D.Yu., Martazanova B.A., Lapina V.S., Korolkova A.I., Martynova M.V., Abubakirov A.N. The transcriptional profile of cumulus cells in women with diminished ovarian reserve in ovarian stimulation protocols in different phases of the menstrual cycle in in vitro fertilization programs. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (12): 68-77. (in Russian)
https://dx.doi.org/10.18565/aig.2017.12.68-77
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