Reproductive Medicine and Biology, 20(4), 524-536, 2021
Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy
Does the OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu (OPTIMUM) treatment strategy, developed for treating repeated implantation failure (RIF), contribute to improving pregnancy outcomes in patients with a history of recurrent pregnancy loss (RPL)?
Methods
Between 2018 and 2019, women with RPL after two or more clinical pregnancy losses underwent RPL testing. We treated chronic endometritis with antibiotics, high Th1/Th2 cell ratios with vitamin D and/or tacrolimus, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. Of 168 consecutive women aged ≤43 years, 115 underwent RPL testing. We compared 100 pregnancies (90 women) and 46 pregnancies (41 women) with and without the OPTIMUM treatment strategy, respectively.
Results
RPL testing identified intrauterine abnormalities in 66 (57.4%), elevated Th1/Th2 cell ratios in 50 (43.5%), thyroid dysfunction in 33 (28.7%), and thrombophilia in 33 (28.7%). The live birth rate in the OPTIMUM group was significantly higher than that in the control group among women aged <40 years (78.1% and 42.3%, respectively; p = 0.002), but no significant difference was observed in women aged ≥40 years (55.6% and 30.0%, respectively; p = 0.09).
Conclusions
The OPTIMUM treatment strategy improved pregnancy outcomes in patients with not only RIF but also RPL.
recurrent pregnancy loss management, OPTIMUM treatment strategy RPL, thyroid function pregnancy loss, thrombophilia recurrent miscarriage, immune modulation implantation failure, uterine milieu optimization, repeated implantation failure treatment, immunotherapy recurrent pregnancy loss, progesterone support miscarriage, autoimmune pregnancy loss protocol
PMID 34646081 34646081 DOI 10.1002/rmb2.12412 10.1002/rmb2.12412
Cite this article
Kuroda, K., Ikemoto, Y., Horikawa, T., Moriyama, A., Ojiro, Y., Takamizawa, S., Uchida, T., Nojiri, S., Nakagawa, K., & sugiyama, R. (2021). Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy. Reproductive medicine and biology, 20(4), 524-536. https://doi.org/10.1002/rmb2.12412
Kuroda K, Ikemoto Y, Horikawa T, Moriyama A, Ojiro Y, Takamizawa S, et al. Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy. Reprod Med Biol. 2021;20(4):524-536. doi:10.1002/rmb2.12412
Kuroda, Keiji, et al. "Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy." Reproductive medicine and biology, vol. 20, no. 4, 2021, pp. 524-536.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY
Infertility is not merely a reproductive inconvenience but frequently signals systemic or hormonal pathology — including polycystic ovarian disease, endometriosis, thyroid dysfunction, and immune abnormalities — each carrying independent health risks beyond failure to conceive. Identifying and treating these underlying conditions reduces long-term morbidity and reframes infertility evaluation as a form of preventive medicine rather than a terminal bypass decision.
Ovarian rejuvenation is an innovative procedure intended to restore ovarian fertility and development during the climacteric and has been used to enhance fertility in women with premature ovarian insufficiency (POI). This retrospective study was conducted to determine the effects of an intraovarian platelet-rich plasma (PRP) injection on ovarian stimulation outcomes in women referred to an in vitro fertilisation centre. This was a retrospective observational study, and the inclusion criteria included women of reproductive age with at least one ovary with a history of infertility, hormonal abnormalities, an absence of a menstrual cycle, and premature ovarian failure. During the patient's first consultation, a detailed reproductive history was recorded, a pelvic scan for ovarian size was conducted, and hormonal analysis for follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol (E2), and luteinizing hormone (LH) was conducted. In the study, 469 women with a history of infertility, hormonal abnormalities, an absence of a menstrual cycle, and premature ovarian failure had hormonal levels recorded up to four months after treatment, and these were included in the study. The volume of peripheral blood required to prepare 6-8 mL of PRP for administration was 40-60 mL. The initial concentration of platelets in the peripheral blood sample was about 25000/µL, whereas the prepared PRP had a concentration of 900.000/µL. A volume of approximately 2-4 mL per ovary, depending on the ovarian volume, was used for the intraovarian injection. PRP intervention had significant effects on FSH concentration at the α = 0.05 level. Statistically significant increases in normal values of FSH and E2were observed for months three and four after the PRP intervention for all age groups. The results of our observational study revealed that a PRP intraovarian injection is associated with improved ovarian tissue and function. Future randomised clinical trials are needed to shed light on the use of PRP in ovarian rejuvenation before offering it routinely in clinical practice.
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