Peri-implantation treatment with TNF-α inhibitor for endometriosis and/or adenomyosis women undergoing frozen-thawed embryo transfer: A retrospective cohort study.

Abstract

Problem: Endometriosis and adenomyosis have common pathogenesis and close relationship, with multi-factors involved in related infertility and IVF failure. They lead to anatomical changes, ovarian reserve reduction, endocrine abnormalities, altered endometrial receptivity and immunological dysfunction. Collective evidence indicate that abnormal function of immune cells and secretion of cytokines are closely related to reproductive outcomes among the women. Some studies showed that increased secretion of tumor necrosis factor alpha (TNF-α) led a key role in pro-inflammatory response in women with endometriosis/adenomyosis.TNF-a is embrryotoxic and receptivity impairing. Therefore, immunotherapy is a targeted therapeutic strategy apart from routine treatment. TNF-α inhibitors such as etanercept and adalimumab were shown to reduce the embryotoxic and anti-inflammatory effects to increase IVF pregnancy rates in recurrent implantation failure or endometrioma patient. However, there's no evidence about the use of adalimumab for patients with endometriosis and/or adenomyosis undergoing Frozen embryo transfer(FET).

Method of study: A retrospective analysis of 141 women with endometriosis and/or adenomyosis undergoing FET from January 2021 to Jun 2023 was conducted.They were 20-42 years old, with or without previous implantation failure. Endometriosis was diagnosed by laparoscopy during their infertility workup and adenomyosis was confirmed by vaginal ultrasound screening. GnRH agonist and hormone replacement treatment (HRT) or HRT were taken for endometrium preparation according to doctor's evaluation and preference. Before and after embryo transfer, 84 women were treated with Adalimumab and 57 patients were untreated. Implantation rate, clinical pregnancy rate, ongoing pregnancy rate and live birth rate were compared between the two groups.

Results: The demographics and baseline characteristics between the two groups were comparable. Stage of embryo transferred and number of embryo transferred were comparable between the two groups (p = 0.227 and p = 0.204 separately). The regimen of endometrium preparation was similar too(p = 0.907). The implantation rate was significantly improved in study group (28.09 % vs 49.18 %, X²=9.515, P = 0.002). The clinical pregnancy rate was much lower in control group comparing with TNF-α inhibitor treatment group (42.11 % vs 60.71 %, X²=4.723, P = 0.029). There was no significant difference between the two groups as for ongoing pregnancy rate (38.60 % vs 52.38 %, X²=2.591, P = 0.107)and live birth rate (36.84 % vs 47.62 %, X²=1.606, P = 0.205). Following adjustment for age, BMI, number of prior failed transfer, stage of embryo transferred in a multiple logistic analysis, patients treated without TNF-α inhibitor had a significant lower CPR (ORadj 0.45, 95 %CI 0.22-0.92, p = 0.029) and a similar probability for OPR (ORadj 0.56, 95 %CI 0.28-1.12) and LBR (ORadj 0.62, 95 %CI 0.31-1.26) as compared with patients with TNF-α inhibitor treatment. However, an obvious trend of improvement of LBR was observed and it's clinical relevant for the patients.

Conclusion: In women with endometriosis and/or adenomyosis, peri-implantation treatment with TNF-α inhibitor increased implantation rate and clinical pregnancy rate significantly compared with control group in FET cycles. The ongoing pregnancy rate and live birth rate were not significant different, while the difference was clinical relevant.