RESEARCH ARTICLE


https://doi.org/10.5005/jp-journals-10016-1324
International Journal of Infertility and Fetal Medicine
Volume 14 | Issue 3 | Year 2023

Does Oral Antibiotic Therapy for Chronic Endometritis Improve Reproductive Outcomes in Assisted Reproductive Technology? A Prospective Cohort Study


Amulya Nagulapalli1https://orcid.org/0009-0002-4889-6363, Hiya Agrawal2, Monna Pandurangi3https://orcid.org/0000-0003-0347-4810, Radha Vembu4https://orcid.org/0000-0003-0543-0600, Sanjeeva R Nellepalli5https://orcid.org/0000-0002-9681-8493

1,3–5Department of Reproductive Medicine and Surgery, Sri Ramachandra Institute of Higher Education & Research, Chennai, Tamil Nadu, India

2Neelkanth IVF, Jodhpur, Rajasthan, India

Corresponding Author: Monna Pandurangi, Department of Reproductive Medicine and Surgery,Sri Ramachandra Institute of Higher Education & Research, Chennai, Tamil Nadu, India, Phone: +91 9841197605, e-mail: monapandurangi@gmail.com

Received on: 11 April 2023; Accepted on: 31 July 2023; Published on: 25 November 2023

ABSTRACT

Background: Chronic endometritis (CE) is a continuous and subtle inflammation of the endometrium caused by bacterial pathogens. It is associated with infertility and poor reproductive outcomes and presents with nonspecific symptoms, making the diagnosis difficult. The gold standard diagnostic criterion is histopathological examination (HPE) and cluster of differentiation (CD) 138 immunohistochemistry (IHC) of endometrial tissue, which is a marker of plasma cells. The effect of antibiotic treatment on reproductive outcomes in Indian infertile women with CE undergoing assisted reproductive technology (ART) has not been extensively studied.

Aim: To investigate the influence of oral antibiotic treatment on reproductive outcomes in women with CE undergoing ART.

Settings and design: Prospective cohort study at a tertiary care teaching hospital.

Materials and methods: A total of 234 infertile women planned for ART underwent endometrial biopsy in the proliferative phase. They were divided into CE-negative (group I) and CE-positive group (group II) based on endometrial biopsy HPE and CD138 IHC. Women in group II received oral antibiotic therapy, and a repeat biopsy was done to assess the cure rate. If CE persisted, they received a second course of antibiotic therapy. They had undergone intracytoplasmic sperm injection (ICSI), and embryo transfer was done where at least one good-grade embryo was transferred. The baseline characteristics and ART outcomes were compared among the two groups.

Statistical analysis: Statistical Package for the Social Sciences (SPSS) 29.0 version, Chi-squared test, one-way analysis of variance (ANOVA), and independent sample t-test.

Results: The baseline characteristics, controlled ovarian stimulation cycle characteristics, and cycle outcomes were comparable among the two groups. No significant difference in cumulative pregnancy rate (p = 0.95), cumulative miscarriage rate (p = 0.21), ongoing pregnancy rate (p = 0.52), and cumulative live birth rate (p = 0.69) was noted between the two groups.

Conclusion: Evaluation and treatment of infertile women undergoing ART for CE is an effective option to improve reproductive outcomes.

Clinical significance: To improve reproductive outcomes in ART, routine screening and timely oral antibiotic treatment for CE is a feasible choice.

How to cite this article: Nagulapalli A, Agrawal H, Pandurangi M, et al. Does Oral Antibiotic Therapy for Chronic Endometritis Improve Reproductive Outcomes in Assisted Reproductive Technology? A Prospective Cohort Study. Int J Infertil Fetal Med 2023;14(3):123–128.

Source of support: Nil

Conflict of interest: Dr Sanjeeva R Nellepalli is associated as the Editorial Board member of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of this editorial board member and his research group

Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.

Keywords: Assisted reproductive technology, Cluster of differentiation 138 immunohistochemistry, Chronic endometritis, Oral antibiotic therapy, Reproductive outcomes

INTRODUCTION

Chronic endometritis (CE) is a state of subtle and continuous inflammation of the endometrium caused by bacterial organisms like Streptococcus, Escherichia coli, Neisseria gonorrhoeae, Chlamydia, Enterococcus, Mycoplasma hominis, Ureaplasma urealyticum, Enterobacteriaceae, Bifidobacteria, Staphylococcus, and Prevotella.1 CE is characterized by prominent features such as endometrial mucosal inflammation, stromal edema, the presence of stromal plasma cells, and stromal cell proliferation.2 Endometrium is usually infiltrated by different types of immune cells like macrophages, natural killer cells, and T- lymphocyte subsets,3 and their mediators play a critical role in endometrial receptivity, which affects implantation of the embryo. In comparison, plasma cells, as well as B-lymphocytes, are scarcely noticed in the endometrium.4 These changes probably impair the endometrial receptivity by various mechanisms5 such as cytokine dysregulation, changes in uterine contractility, altered vascularization, modified decidualization, and disrupted autophagy. CE is usually asymptomatic in one-third of the cases or presents with vague symptoms like chronic pelvic pain, persistent leukorrhea, abnormal uterine bleeding, or dyspareunia,6 posing a challenge for physicians in diagnosing CE. According to a few studies, CE interferes with spontaneous pregnancies and assisted reproductive technology (ART) pregnancy outcomes7-9 leading to recurrent pregnancy losses, recurrent implantation failures, obstetrical complications10 like preterm labor, decreased term live birth rate per pregnancy, and neonatal complications such as periventricular leukomalacia and cerebral palsy.11 The estimated prevalence of CE varied due to differences in the diagnostic criteria used in various studies. In the general population, the prevalence is between 0.8 and 19%,12 in the infertile population; the prevalence is between 3 and 44%,13 in infertile women with unexplained recurrent miscarriage, it ranges from 8.9 to 56.1%14 and in women with repeated implantation failures prevalence ranges from 14 to 57%.14 Currently, there are no well-established guidelines or consensus proposed for diagnosing CE. Identification of stromal plasma cells in histopathological examination (HPE) of endometrial tissue is the gold standard criterion for diagnosing CE.15 But diagnosis of plasma cells solely by routine Haematoxylin and Eosin staining is difficult, and hence immunohistochemical (IHC) staining with CD 138, which is a marker for transmembrane heparan sulfate proteoglycan (syndecan-1) on the surface of a plasma cell is a more efficient method for diagnosing CE.16 The treatment for CE, whether to treat or not, is still debatable. Antibiotic treatment was successful in eliminating plasma cells in the endometrial stroma in patients with CE. The treatment is empirical, and doxycycline being a broad-spectrum anti-bacterial, is preferred as well as a first-line drug of choice. Ciprofloxacin and metronidazole are used as second-line treatments.9,11,17 In cases of multi-drug resistance, persistent CE azithromycin or moxifloxacin or clindamycin was used for treatment.17 There is a lack of data regarding CE prevalence in the infertile Indian population and the effect of oral antibiotic treatment on ART outcomes in women with CE. Earlier studies on the role of oral antibiotic treatment in CE on ART outcomes were confined to women who had recurrent implantation failure and unexplained recurrent loss of pregnancy. Therefore, the aim of our study is to investigate the influence of oral antibiotic treatment for CE on reproductive outcomes in women with CE undergoing ART.

MATERIALS AND METHODS

Study Population

This is a prospective cohort study conducted in the Department of Reproductive Medicine and Surgery of a tertiary care university hospital from January 2019 to October 2022. A total of 234 infertile women who had endometrial biopsy during saline infusion sonohysterography (SIS) or hysteroscopy as a part of cavity evaluation prior to ICSI were recruited. Inclusion criteria were females aged between 21 and 45 years undergoing ART, where at least one good-grade embryo was available for transfer. Patients with uncorrected submucosal fibroid or intramural fibroid >5 cm, uncorrected uterine cavity malformation like septum, endometrial polyp, intrauterine adhesions, and previous history of genital tuberculosis were excluded from the study.

The methodology of the study is depicted in Flowchart 1.

Flowchart 1: Flow diagram of the study

Sample Size

The calculated sample size was 116. Approval for the study was obtained from the Institutional Ethical Committee (CSP-MED/19/JAN/49/13). Written and well-informed consent was obtained from the patients recruited for the study.

Methodology

Infertile women fulfilling the selection criteria were recruited in the study. Endometrial sampling was performed using a Probet biopsy catheter (Gynétics®, Belgium) during SIS as an outpatient procedure or along with hysteroscopy as an inpatient procedure during the proliferative phase of the menstrual cycle (days 7–11). The endometrial biopsy samples were sent in formalin for HPE and cluster of differentiation (CD138) IHC (Flowchart 1).

Criteria for Diagnosis of CE

Chronic endometritis (CE) was defined as the histological presence of either at least one endometrial stromal plasma cell in the entire section on HPE or ≥ 5 CD138 positive cells/HPF on IHC.18 Single experienced pathologists examined all the specimens. Based on the endometrial biopsy report, all the patients were grouped into:

  • Negative for CE: Group I

  • Positive for CE: Group II

Antibiotic Treatment

Chronic endometritis (CE) positive women were prescribed oral antibiotics doxycycline (100 mg twice daily for 14 days) followed by a combination of ciprofloxacin + tinidazole (500 mg ciprofloxacin and tinidazole 600 mg twice daily for 14 days) (ciplox-TZ, Cipla® Limited, Mumbai, India). Subsequently, endometrial sampling was repeated after completing a course of antibiotics in the next proliferative phase of the menstrual cycle by Probet biopsy catheter on an outpatient basis and histologically reassessed for cure rate. Depending on the repeat biopsy report, women were divided into:

  • Cured CE group: CE negative histologically—group II1

  • Persistent CE group: CE positive histologically—group II2

Women in the persistent CE group received a second course of oral antibiotics—tablet clindamycin 300 mg (twice a day for 14 days). Women underwent controlled ovarian hyperstimulation (COH) with antagonist protocol, and embryo transfer was done with at least one good-grade embryo.

Protocols for COH and Embryo Transfer

Controlled ovarian hyperstimulation (COH) was done using antagonist protocol. On day 2 of cycle, COH with recombinant follicular stimulating hormone (rFSH, Gonal F®, Merck Serono SA, Switzerland) or urinary FSH (Folliculin™, Bharath Serum and Vaccines Limited, India) ± human menopausal gonadotropin (Gynogen® HP, Sanzyme Private Limited, Hyderabad, India) was started, and the dose was individualized for each patient according to age, body mass index (BMI), AFC, anti-Mullerian hormone (AMH), and/or previous response to ovarian stimulation. Flexible GnRH antagonist (cetrorelix 0.25 mg/day subcutaneous–Asporelix™ 0.25 mg, Bharath Serum and Vaccines Limited, India) was started when the leading follicle was ≥14 mm till the day of trigger. Follicular monitoring was done daily or on alternate days based on the response to stimulation, and the gonadotropin dose was adjusted accordingly. Ovulation trigger was given when two or more follicles are ≥18 mm, either with urinary human chorionic gonadotropin (HCG) 10000 IU IM or GnRH agonist trigger in patients with hyper-response or high risk for ovarian hyperstimulation syndrome (OHSS) or dual trigger. Retrieval of oocytes was done 34–36 hours after trigger under transvaginal ultrasound (TVS) guidance. Fertilization was done with intracytoplasmic sperm injection (ICSI) in all patients. They underwent either fresh or frozen embryo transfer as per institutional protocol. Women undergoing fresh embryo transfer were supplemented with estradiol valerate twice daily (Progynova® 2 mg, Bayer Zydus Pharma AG, Germany) and Inj micronized progesterone 100 mg (Susten® 100, Sun Pharma Laboratories Limited, Mumbai, India) intramuscularly/day was started on the day of retrieval for 3 days in cleavage stage embryo transfer and 5 days for blastocyst transfer. Embryo transfer was performed by utilizing ultrasound and a Cook catheter (Cook Medical, Bloomington, United States of America). Luteal support was given in the form of micronized vaginal progesterone 200 mg (Susten® 200, Sun Pharma Laboratories Limited, Mumbai, India) thrice daily and dydrogesterone 10 mg (Duphaston®, Abott India Limited, Puducherry, India) thrice daily orally.

In women undergoing frozen embryo transfer either direct hormone replacement therapy (HRT) or suppressed cycle HRT was performed based on patient characteristics. In suppressed cycle HRT, pituitary suppression was achieved with a combined oral contraceptive pill (ethinyl estradiol 0.03 mg + levonorgestrel 0.15 mg) given from 2nd or 3rd day of the next menstrual cycle after oocyte retrieval and injection of leuprolide acetate depot 3.75 mg subcutaneously was given on day 14. After withdrawal bleeding, on day 5 of the cycle, HRT was started with 4 mg of estradiol valerate per day for 5 days, followed by 6 mg for 6 days in suppressed cycle HRT and in direct HRT cycles from day 2/3 estradiol valerate 6 mg per day was started. Endometrial thickness (ET) and pattern were assessed by TVS. Estradiol valerate dose was adjusted till ET ≥8 mm, and luteal support was given as in fresh embryo transfer. Serum-β HCG was done 2 weeks after embryo transfer, and if it was ≥5 mIU/mL, TVS was performed 4 weeks post-embryo transfer to assess for viability and luteal support was continued till 10 weeks. All women were followed for a maximum of three embryo transfer cycles from conception till delivery.

Definition of Reproductive Outcomes

Serum β-HCG of ≥5 mIU/mL is defined as pregnancy. Clinical Pregnancy is defined as the detection of an intrauterine gestational sac with cardiac activity on TVS. The live birth rate is defined as the birth of at least one newborn after 24 weeks. Miscarriage was defined as pregnancy loss during the first trimester. The ongoing pregnancy rate is defined as pregnancy continuing beyond 20 weeks. The cumulative pregnancy rate (number of patients with β -HCG positive/total number of embryo transfers), cumulative clinical pregnancy rate (number of patients with detection of intrauterine gestational sac with cardiac activity on TVS/total number of embryo transfers), cumulative miscarriage rate (number of miscarriages/total number of pregnancies in three embryo transfers), and cumulative live birth rate (number of deliveries that resulted in live born neonate after 24 weeks expressed per 100 embryo transfers up to three FET cycles) were recorded.

Statistical Analysis

IBM Statistical Package for the Social Sciences (SPSS)® Statistics software for Windows, version 29.0, was used for the purpose of analysis of our collected data. The categorical variables were represented with the help of frequency analysis as well as percentage analysis. Mean ± standard deviation (SD) was used to report continuous variables. Independent sample t-test was used to determine the significant difference amongst the samples of different groups having two variables. A one-way analysis of variance (ANOVA) test was used for the groups having multi-variate samples. The Chi-squared test and Fisher–Irwin Test were used to evaluate the significant difference among the qualitative categorical variables. A p-value of <0.05 was considered statistically significant.

RESULTS

A total of 234 infertile women undergoing ART were recruited as per the study criteria. Among 234 infertile women who underwent endometrial biopsy, 27.4% (64/234) were positive for CE (group II). Hence, the prevalence of CE in an infertile population undergoing ART is 27.4%. Women in group II, after the first course of antibiotic therapy, had repeat endometrial biopsy. CE was negative in 73.4% (47/64) (group II1), and CE was persistently positive in 26.6% (17/64) (group II2) after repeat endometrial biopsy. Therefore, the cure rate for CE was 73.4% (47/64) after the first course of antibiotic therapy.

The baseline characteristics among the two groups were comparable, as depicted in Table 1. The characteristics of the COH cycle and its outcomes were comparable among the two groups. No significant difference was noted, as shown in Tables 2 and 3.

Table 1: Baseline characteristics
Baseline characteristics Whole cohort (n = 234) Group I (n = 170) Group II (n = 64) p-value
Age (years)a 31.4 ± 4.7 31.6 ± 4.7 30.8 ± 4.59 0.262
BMI (kg/m2)a 26.8 ± 4.7 26.8 ± 4.7 26.6 ± 4.8 0.763
Duration of infertility (years) a 6.6 ± 3.8 6.7 ± 3.8 6.4 ± 3.6 0.485
Type of infertility
 Primary infertilityb 67.1% 67.1% 67.2% 0.985
 Secondary infertilityb 32.9% 32.9% 32.8%
Indication for ART
 Female factor infertilityb 37.2% 40% 29.7% 0.183
 Male factor infertilityb 29.1% 27.6% 32.8%
 Combined factor infertilityb 26.5% 25.9% 28.1%
 Unexplained infertilityb 7.3% 6.5% 9.4%
Ovarian reserve test
 AMHa 3.66 ± 2.9 3.4 ± 2.48 4.4 ± 3.9 0.078
 Antral follicle count (AFC)a 20.0 ±10.9 20.07 ± 11.26 19.84 ± 9.8 0.893

a, mean ± SD; b, %

Table 2: Cycle characteristics
COH cycle characteristics Whole cohort (n = 207) Group I (n =150) Group II (n = 57) p-value
The total dose of gonadotropins 3588.8 ± 2428.3 3862.4 ± 2696.8 3332.02 ± 1460.3 0.161
Days of stimulationa 10.2 ± 1.96 10.3 ± 2.06 10.1 ± 1.7 0.385
The number of metaphase II oocytes retrieveda 10.0 ± 6.4 10.1 ± 6.44 10.3 ± 6.2 0.818
Total number of embryosa 8.1 ± 5.6 8.0 ± 5.55 8.2 ± 5.6 0.809
Number of grade I embryosa 4.8 ± 3.6 4.83 ± 3.3 5.04 ± 3.9 0.766

a, mean ± SD

Table 3: Cycle outcomes
Embryo transfer parameters Whole cohort (n = 234) Group I (n = 170) Group II (n = 64) p-value
Total number of embryo transfers 300 222 78
Fresh embryo transferb 8.3% 8.1% 8.9% 0.812
Frozen embryo transferb 91.7% 91.9% 91.1%
ETa 9.35 ± 1.65 9.35 ± 1.58 9.35 ± 1.84 1.00
Number of embryos transferreda 2.75 ± 0.78 2.74 ± 0.78 2.79 ± 0.78 0.626

a, mean ± SD; b, (%)

A total of 234 women were followed for a maximum of three embryo transfer cycles from conception to delivery. No significant difference was noted between the two groups in reproductive outcomes (Table 4).

Table 4: Reproductive outcomes
Reproductive outcomes Group I (n = 234) Group II (n = 64) p-value
Cumulative pregnancy rate 51.8% 53% 0.951
Cumulative clinical pregnancy rate 49.2% 50.3% 0.880
Cumulative miscarriage rate 14.3% 9.1% 0.208
Ongoing pregnancy rate 6.7% 8.9% 0.518
Cumulative live birth rate 30.5% 33% 0.691

DISCUSSION

This prospective cohort study has evaluated the CE prevalence in infertile Indian women undergoing ART and showed treatment with oral antibiotics might improve outcomes of pregnancy among women who were diagnosed with CE and underwent ART.

The diagnosis of CE in this study was made using the histological presence of either at least one endometrial stromal plasma cell in the entire section on HPE or ≥5 CD138 positive cells/HPF on IHC. We used IHC along with HPE, as identification of plasma cells with only HPE is difficult due to infiltration of monocytes, mitosis of stromal cells, and plasma cell-like appearance of stromal cells, along with plasma cells in endometrial specimens. IHC staining has lower intra- and interobserver variability and is a specific and reliable method for diagnosing CE. The timing of endometrial biopsy was during the proliferative phase, as the studies concluded increased CE prevalence in the proliferative phase as compared to the secretory phase.7,8,14

Screening for CE can also be done by hysteroscopy, and the findings suggestive of CE include19,20 presence of focal or diffuse hyperemia flushed with white central points, stromal edema, and micro polyps (smaller than 1–2 mm). The sensitivity and specificity varied from 40 to 100% and 56 to 92.5%, respectively, for hysteroscopy with the use of CD138 IHC as the reference standard.20 The advantage of hysteroscopy is it helps in obtaining site-specific biopsies, thus increasing the probability of detection of CE. But, stand-alone, it cannot replace HPE and CD138 IHC for diagnosis of CE. We did not include hysteroscopic findings to diagnose CE in our study as not all patients underwent hysteroscopy for cavity evaluation prior to ART.

Other methods like endometrial tissue microbial culture for diagnosis of CE have been proposed. It helps in the detection of pathogens and also antibiotic treatment according to drug sensitivity testing. The main disadvantage of the culture is the long turnaround time; not all organisms are culturable,21 and contamination of biopsy by vaginal secretions leads to unreliable results. Newer methods for the identification of CE by molecular microbiology are the detection of nine CE pathogens in endometrial samples by real-time polymerase chain reaction and next-generation sequencing (NGS). The advantage of this method is that it is fast and helps in detecting both culturable and nonculturable endometrial pathogens causing CE.1 The main limitation of the test is it’s expensive and has low negative predictive value.1 The CE prevalence in our study who underwent ART is 27.4%. Similar prevalence was reported in studies done by Liu et al.13 ~ 31.50% (1261/4003), Chen et al.22 ~ 27.9% (26/93), Xiong et al.18 ~ 37% (237/640). In contrast, Kasius et al.23 reported a lower prevalence of 2.8% (23/85) as in this study, the diagnosis was based solely on the identification of plasma cells on hematoxylin and eosin staining, and CD138 IHC was reserved when the diagnosis was doubtful.

Unexplained cause of infertility as an indication for ART was seen in 7.3% (17/234) in our study, which is lower when compared to the study done by Cicinelli et al.,7 where unexplained factor was seen in 56.8% of women as they included both hysteroscopy and histology for the diagnosis of CE. As previous studies8,9,12 have indicated a better cure rate after two courses of antibiotics, to avoid multiple endometrial biopsies and to decrease the financial burden, we gave a prolonged course of multiple antibiotics as the first line. The cure rate was 73.4% (47/64) in our study. Comparable cure rates were noted in a study done by Xiong et al.,18 which was 89.0% (211/ 237).RCT done by Song et al.24 showed cure rate for CE was 89.83% (53/59) as compared to a cure rate of 12.73% (7/55) is not treated group and in a study done by Liu et al.,13 the cure rate for CE was 79.1% (733/927). A case-control study done by Luncan et al.25 concluded that intrauterine antibiotic infusion had a significantly better cure rate for CE (89.29%, 25/28) than oral triple-antibiotic therapy (45.83%, 11/24). The cure rate varied among different studies due to different diagnostic criteria and antibiotic regimens. The reproductive outcomes in group I was comparable to group II. This shows that proper screening and timely antibiotic treatment prior to embryo transfer can improve ART outcomes in CE positive group. When a subgroup analysis in reproductive outcomes was done, and they were divided into three groups I, II1, and II2, similar cumulative pregnancy rates (51.8 vs 54 vs 47.1%, p = 0.871), cumulative clinical pregnancy rate (49.2 vs 51.4 vs 47.1%, p = 0.938), cumulative miscarriage rate (14.3 vs 12.4 vs 0%, p = 0.187), cumulative live birth rate (30.5 vs 31.2 vs 38.2%, p = 0.790), and ongoing pregnancy rate (6.7 vs 10.5 vs 4.7%, p = 0.557) noted in groups I, II1, and II2, respectively. Xiong et al.18 demonstrated that antibiotic treatment improved reproductive outcomes in CE-positive women but in women with persistent CE had significantly reduced pregnancy outcomes in frozen embryo transfer cycles. In our study, the reproductive outcomes were comparable in cured CE and persistent CE groups. This variation can be because a different antibiotic regimen was used in the Xiong et al. and the small sample size in the persistent CE group in our study. Another study done by Liu et al.13 concluded that antibiotic treatment improved reproductive outcomes in women with CE, and endometrial re-biopsy after antibiotic treatment to test for a cure had no effect on pregnancy outcomes. Song et al.24 conducted an RCT between the CE antibiotic-treated group and CE not treated group; even though the cure rate was significantly high in the treated CE group (89.3%) than CE not treated group (12.7%), there was no clear evidence whether oral antibiotic therapy improved pregnancy outcomes. The discrepancy between the RCT and our study was the distinct diagnostic criteria used for CE and antibiotic regimen. The cumulative miscarriage rate in our study in the persistent CE group is 0%; it may be due to the smaller sample size in that group, though it is not statistically significant. The strengths of our study are: a prospective study, all the samples were obtained during the proliferative phase of the cycle, and at least one good-grade embryo was transferred in all embryo transfer cycles. The limitations of the study include a single-center study, the observational nature of the study, and hysteroscopic findings were not included in diagnosing CE, and the small sample size in the persistent CE group. There was no control group where antibiotic treatment was not given in women with CE. Future multi-center, randomized control trials with uniform diagnostic criteria for CE and antibiotic regimen are required to confirm the findings of our study and to know the impact of antibiotic treatment on reproductive outcomes in women undergoing ART. We need more studies on newer methods for the identification of CE by molecular microbiology in endometrial samples by RTPCR and NGS and also studies comparing intrauterine antibiotic infusion and oral antibiotic therapy for treating CE.

CONCLUSION

Evaluation and treatment of infertile women undergoing ART for CE is an effective option to improve ART outcomes.

Clinical Significance

To improve reproductive outcomes in ART, routine screening along with timely treatment of CE with oral antibiotics is a feasible choice.

ORCID

Amulya Nagulapalli https://orcid.org/0009-0002-4889-6363

Monna Pandurangi https://orcid.org/0000-0003-0347-4810

Radha Vembu https://orcid.org/0000-0003-0543-0600

Sanjeeva R Nellepalli https://orcid.org/0000-0002-9681-8493

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