Management of chronic endometritis before in vitro fertilization: lights and shadows

Reflections
Management of chronic endometritis before in vitro fertilization: lights and shadows
Like

Please sign in or register for FREE

Your Fertility and Sterility Dialog login information is not the same as your ASRM or EES credentials. Users must create a separate account to comment or interact on the Dialog.

Go to the profile of shijuanzi
6 months ago

Dear Editor,

We truly appreciate Cicinelli et al. from Italy for their comprehensive evaluation on our article (1) and welcome this opportunity to respond to their comments.

The writers question the histologic criterion for diagnosis of chronic endometritis (CE) in the current study. According to the published studies (2), we adopted ≥ 1 plasma /CD138+ cell per 10 high power fields (HPFs) as criteria. In our work, CE was diagnosed through hysteroscopy and confirmed by histology and immunohistochemistry CD 138. Although presence of plasma cells within the endometrial stroma is the most useful histologic criterion for diagnosis of CE, the strict cutoff infiltration of plasma cells remains undetermined. A new of diagnostic criteria was recently introduced that CE be defined as the presence of one or more plasma cells per 10 HPFs in the setting of endometrial stromal changes, such as spindling of cells, edema, breakdown, pigment deposition, areas of hypercellularity, and presence of inflammatory cells other than plasma cells (3). 

Another question, posed by the authors is on our methods for ascertaining CE cure. During the study period, CE women were asked to have a repeat hysteroscopic evaluation instead of blind endometrial biopsy. On the one hand, through a inspection of the entire uterine cavity, hysteroscopy allows identifying focal lesions and targeted biopsies. Blind biopsy may underestimate the disease (tissues were obtained from normal areas). On the other hand, hysteroscopy has been proved with higher negative negative predictive value of CE diagnosis by comparing hysteroscopy with the histological analysis of endometrial samples. Moreover, previous studies also shown a high correlation between the hysteroscopic signs of CE and success rates in patients undergoing IVF. When a diagnostic hysteroscopy shows a negative result for CE, it is highly suggested restoration of a normal endometrium. Future studies evaluating the optimal test of cure are necessary. Given the limitations, we discussed in our paper that caution should be warranted in interpretation of this specific outcome. 

In terms of spontaneous abortion rates, we found that patients cured with antibiotic therapy continued to have higher risk of spontaneous abortion. While CE is cured with antibiotic treatment, whether the subsequent reproductive outcomes improve after the cure of CE remains a concern. Consistent with our findings, a previous study suggested that despite successful treatment, patients with history of CE had a lower pregnancy outcomes. Pregnancy rates after endometrial receptivity analysis and personalized ET in the non‐CE, CE, and cured CE groups were 77.8%, 22.2% and 51.7%, respectively (4). The information is valuable for counselling IVF patients with previous CE, especially when antibiotic administration occurring prior to ovarian stimulation. Cure of CE has been previous reported to increase the chance of live birth in infertile women, however, the analyses were small and restricted to couples with recurrent pregnancy loss or repeated implantation failure. Whether the results can be extrapolated to the general population of women with infertility is unclear. A retrospective study by Xiong et al. (5) including 640 women undergoing frozen-thawed embryo transfer (ET) cycles showed that antibiotic treatment was an effective way to improve the reproductive outcomes of women with severe CE (CD138/HPF5). However, they took women with mild CE (CD138/HPF≤ 4) as the control group, which makes it difficult to interpret the treatment effects. 

CE may represent some more complex endometrial abnormality which does not change with antibiotic administration. It has been reported that CE was caused by a multifaceted approach involving hormonal, infectious, fibrotic, and autoimmune factors (6). Lack of knowledge about the precise mechanism of inflammation related to pregnancy loss is still one of the challenges. We hope our study creates discussion about the the impact of CE and its treatment on future reproductive outcomes in infertile couples.

References

  1. Duan H, Li X, Hao Y, Shi  J, Cai H. Risk of spontaneous abortion after antibiotic therapy for chronic endometritis prior to IVF/ICSI stimulation. Fertil Steril. 2022; 118: 337-46.
  2. Song D, He Y, Wang Y, Liu Z, Xia W, Huang X, et al. Impact of antibiotic therapy on the rate of negative test results for chronic endometritis: a prospective randomized control trial. Fertil Steril 2021;115;1549-56
  3. McQueen DB, Maniar KP, Hutchinson A, Confino R, Bernardi L, Pavone ME. Redefining chronic endometritis: the importance of endometrial stromal changes. Fertil Steril202;116:855-61.
  4. Kuroda K, Horikawa T, Moriyama A, Nakao K, Juen H, et al. Impact of chronic endometritis on endometrial receptivity analysis results and pregnancy outcomes. Immun Inflamm Dis. 2020;8:650-8.
  5. Xiong Y, Chen Q, Chen C, Tan J, Wang Z, Xu Y, et al. Impact of oral antibiotic treatment for chronic endometritis on pregnancy outcomes in the following frozen-thawed embryo transfer cycles of infertile women: a cohort study of 640 embryo transfer cycles. Fertil Steril 2021;116:413-21.
  6. Drizi A, Djokovic D, Lagan a AS, van Herendael B. Impaired inflammatorystate of the endometrium: a multifaceted approach to endometrial inflammation. Current insights and future directions. Prz Menopauzalny 2020;19: 90-100.

He Cai, M.D., Juanzi Shi, M.D., Ph.D.

Reproductive Medicine Center, Northwest Women’s and Children’s Hospital, Xi’an, China.

Go to the profile of Pandiyan  Natarajan
5 months ago

Chronic Endometritis is a non se.qui.tur.

I read with great interest the Reflections on Chronic Endometritis. I am a Gynecologist for the last 45 years and in Full time Infertility and Assisted Reproduction for 37 years. I am yet to see a true case of Chronic Endometritis, other than Tuberculosis Endometritis.  I worked/work in 4 countries in tertiary referral centers. We never had a case referred to us as Chronic Endometritis. This discussion reminded me of the discussion we had in the past about Luteal Phase Defect( LPD) and Anti sperm antibodies. Luckily ASRM has put an end to this debate by emphasizing the continued clinical irrelevance of LPD. “Present limited data do not support LPD as a clinical entity that causes infertilityor early pregnancy loss, or that treatment can improve clinical outcomes.” (1) Anti sperm antibodies Testing is rarely if ever done these days and seems to have had a Natural death.

Chronic Endometritis is a Nebulous entity. Diagnostic features are vague and ill defined. Treatment methods are not standardized and the outcome is uncertain and the influence of the condition on Fertility is unproven. Under the circumstances, diagnosis and treatment of CE has no clinical realm. 

1. Diagnosis and treatment of luteal phase deficiency:
a committee opinion.  (Fertil Steril 2015;103:e27–e32). (Fertil Steril! 2021;115:1416–23.

Professor Dr Pandiyan Natarajan,

Chief Consultant in Andrology and Reproductive Sciences,

Apollo 24/7, NOVA IVF FERTILITY,

 Chettinad Super Speciality Hospital (Retired),

Professor Emeritus, The Tamil Nadu Dr MGR Medical University