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Therapeutics Metabolic and Endocrine Agents

Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy

Kuroda K, Ikemoto Y, Horikawa T, Moriyama A, Ojiro Y, Takamizawa S, Uchida T, Nojiri S, Nakagawa K, Sugiyama R

Published October 15, 2021 Reproductive Medicine and Biology, 20(4), 524-536
DOI 10.1002/rmb2.12412 PMID 34646081 PMC PMC8499598

RRM Academy Synopsis

Recurrent miscarriage testing linked to more live births under age 40

In a retrospective study of women with two or more pregnancy losses at one Tokyo clinic, women under 40 who had testing and treatment had live births in about 8 out of 10 pregnancies. Under-40 women without testing had about 4 out of 10 (p = 0.002). Women 40 and older showed no significant difference.

Live birth per pregnancy, under age 40: Tested and treated, 78.1 in 100; Not tested, 42.3 in 100
Live birth per pregnancy, under age 40: Tested and treated, 78.1 in 100; Not tested, 42.3 in 100. Source: Kuroda K et al., 2021, PMID 34646081.
Study at a glance, cohort study of 115 tested women: Recurrent miscarriage testing linked to more live births under age 40
Study at a glance, cohort study of 115 tested women: Recurrent miscarriage testing linked to more live births under age 40. Source: Kuroda K et al., 2021, PMID 34646081.

Key Findings

  • Uterine abnormalities were the most common finding among the 115 tested women (66 women, 57.4%), ahead of elevated Th1/Th2 cell ratios (50, 43.5%), thyroid dysfunction (33, 28.7%) and thrombophilia (33, 28.7%).
  • Sixty women (52.2%) had two or more of these risk factors, including 5 (4.3%) with all four. Eleven women (9.6%) had none.
  • Under age 40, live birth per pregnancy was 78.1% (50 of 64) with the OPTIMUM treatment strategy and 42.3% (11 of 26) without it (p = 0.002).
  • At age 40 and older, live birth per pregnancy was 55.6% (20 of 36) with the strategy and 30.0% (6 of 20) without it (p = 0.09).
  • Among 90 women, a first-pregnancy live birth went with no infertility (OR = 13.83, 95% CI = 1.76–108.95) and younger age (OR = 1.22, 95% CI = 1.06–1.40) in single-factor analysis.

Interpretation

This cohort study followed women with recurrent pregnancy loss at one clinic in Tokyo. Testing and treatment was linked with a higher live birth rate in women under 40. The authors note that some women in the comparison group declined testing or were not offered it, which may have introduced selection bias. The findings support larger studies of this testing and treatment strategy.

RRM Context

Restorative reproductive medicine starts with evaluation: find the cause before treating. Only 11 of 115 tested women had no risk factor. The authors report that at least 50% of women with recurrent pregnancy loss have none found on common screening. Losses labeled undiagnosed may have a findable cause.

Our editorial summary of this paper, not the article's abstract.

Abstract

Purpose

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.

Read the guide

Topics

Related research

Therapeutics › Metabolic and Endocrine Agents › Thyroid Replacement · Infertility › Recurrent Pregnancy Loss › Immune and Thrombophilia Factors · Pregnancy › Pregnancy Complications › Intrauterine Infection
Keiji Kuroda, Yuko Ikemoto, Takashi Horikawa, Azusa Moriyama, Yuko Ojiro, Satoru Takamizawa, Toyoyoshi Uchida, Shuko Nojiri, Koji Nakagawa, Rikikazu Sugiyama
K Kuroda, Y Ikemoto, T Horikawa, A Moriyama, Y Ojiro, S Takamizawa, T Uchida, S Nojiri, K Nakagawa, R Sugiyama
PMID 34646081 34646081 DOI 10.1002/rmb2.12412 10.1002/rmb2.12412 Kuroda et al. 2021, Kuroda 2021

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