Is it necessary to perform a routine hysteroscopy before first embryo transfer in patients with previous ectopic pregnancy history: A propensity score matching analysis?

doi:10.21203/rs.3.rs-4658682/v1

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Research Article

Is it necessary to perform a routine hysteroscopy before first embryo transfer in patients with previous ectopic pregnancy history: A propensity score matching analysis?

https://doi.org/10.21203/rs.3.rs-4658682/v1

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Purpose

To determine whether an office hysteroscopy is required before the first embryo transfer in infertile women with previous ectopic pregnancy history.

Methods

Consecutive patients with previous ectopic pregnancy history were categorized into two groups based on the performance of hysteroscopy. Subgroup 1 consisted of patients whose endometrial pathology was normal, subgroup 2 who were diagnosed with endometrial polyps (EP), and subgroup 3 diagnosed with chronic endometritis (CE). Demographics, baselines of characteristics, and pregnancy outcomes after embryo transfer were compared among these groups.

Results

A total of 614 patients were enrolled. No differences were observed in the baseline characteristics of these groups. The clinical pregnancy rates were comparable between hysteroscopy group and non-hysteroscopy group. The spontaneous miscarriage rate was greater in the cured CE subgroup compared to the normal and EP subgroups. Consequently, the live birth rate was comparatively lower in the cured CE group than in both the control group and the EP group.

Conclusions

We found a high pregnancy loss rate in women with CE-confirmed immunohistochemically. While office hysteroscopy serves as a valuable diagnostic instrument, it is imperative that it be supplemented with appropriate and adequate antibiotic therapy. Further investigation is still required before it can be considered a standard infertile workup before the first embryo transfer in patients with previous ectopic pregnancy history.

Trial registration

N/A.

Hysteroscopy

ectopic pregnancy history

reproductive techniques

embryo transfer

Ectopic pregnancy remains one of the most common gynecological emergencies and the leading cause of maternal mortality during the early stages of pregnancy, impacting 1–2% of cases(1). Ectopic pregnancy is defined as the occurrence of a pregnancy outside the uterine cavity, most commonly within the fallopian tube (96%)(2). There are no identifiable risk factors in as much as 50% of cases. Tubal ectopic pregnancy is characterized by several established risk factors, including alterations in the tubal environment, compromised embryo-tubal transport within the fallopian tube, smoking habits, as well as advanced maternal age(3–5). Previous studies exploring the impact of different interventions for ectopic pregnancy on fertility outcomes have yielded inconsistent results. A majority of these studies found that there was no significant difference in the rate of subsequent pregnancy, the risk of recurrent ectopic pregnancy, or the mean duration to the next conception between expectant treatment, MTX administration, and salpingectomy(6, 7).

With increasing focus on reproductive outcomes for patients with ectopic pregnancy history undergoing assisted reproductive technology (ART), it is crucial to elucidate the impact of each treatment method on pregnancy outcomes. This will guide individuals with fertility concerns and a history of ectopic pregnancy in choosing the most appropriate therapeutic approach and preventative measures against the recurrence of ectopic pregnancy.

Previous studies have examined and compared the different embryo stages, transfer cycle, time to pregnancy, and ectopic pregnancy treatments(8–10). Nevertheless, there is currently no available date regarding the application of hysteroscopy to the uterine environment before embryo transfer. The assessment of the uterine cavity appears to be a fundamental component in the examination of all infertile women, given that it is believed that the uterine cavity and its lining, the endometrium, are crucial for embryo implantation(11). Major uterine cavity abnormalities can indeed be found in 10–15% of infertile women, and the most common acquired uterine cavity abnormality is endometrial polyps(EP), which are benign endometrial stalk-like mass protrudes into the uterine cavity and can harm fertility(12). Another uterine abnormality is chronic endometritis(CE), which is a persistent inflammatory condition of the endometrium that is histologically diagnosed by the presence of plasma cells in the stroma of the endometrium(13). CE is attracting attention due to its potential association with infertility of unknown etiology, repeated implantation failure, recurrent pregnancy loss, and several maternal/neonatal complications(14, 15) and is detected in approximately 30%-60% of infertile women with a history of repeated implantation failure (RIF)(16). Although evidence indicates the effectiveness of antibiotic administration to cure CE, the impact of CE and its treatment on reproductive outcomes remains a concern(13). Some researchers showed that CE cured with antibiotic therapy still was associated with an increased risk of spontaneous miscarriage among women undergoing IVF/ICSI treatment(17).

Various techniques are employed to detect abnormalities in the uterine cavity, including transvaginal ultrasonography (TVS), hysterosalpingography (HSG), saline hysterosonography, magnetic resonance imaging (MRI), and hysteroscopy. Hysteroscopy is widely considered the gold standard procedure for the assessment of the uterine cavity due to its ability to provide direct visualization of the uterine cavity(18). To the best of our knowledge, there was no study investigating whether hysteroscopy administration enhances pregnancy outcomes in infertile women with previous ectopic pregnancy history. In the present study, the objective of the current study was to determine whether it is necessary to perform a hysteroscopy to evaluate the uterine cavity before the first embryo transfer in patients with previous ectopic pregnancy history.

Study population

This study was conducted at West China Second University Hospital and was approved by the Ethics Committee of West China Second University Hospital. All patients undergoing ART treatment in our center provided written informed consent for the use of their medical record data for research purposes. Additionally, all patients were registered in the data management system, which stores the medical information of patients seeking to conceive through ART.

We screened retrospectively all women treated at our center for ART treatment between January 2018 and December 2022. Inclusion criteria for participation were patients with a history or histories of tubal ectopic pregnancy treated by surgery or conservative treatment before ART undergoing the first fresh or frozen embryo transfer cycle. The exclusion criteria were as follows: (1) the previous ectopic pregnancy following ART, (2) oocyte donor cycles, (3) the cycles involving preimplantation genetic diagnosis and screening; and (4) any abnormal findings by ultrasound before embryo transfer. Before the initiation of IVF/ICSI-ET treatment, each patient provided written informed consent permitting the collection and analysis of their clinical data. We gathered baseline characteristics including maternal age, body mass index, duration of infertility, basal serum levels of FSH, LH, and E2, count of antral follicles (AFC), cause of infertility, stimulation protocol employed, duration of stimulation, parity status, and the presence or absence of preexisting conditions such as pelvic inflammatory disease. We also recorded the type of ectopic pregnancy treatment (salpingectomy, salpingostomy, or conservative treatment) that was administered. The parameters assessed for IVF cycles included the number of retrieved oocytes, methods of fertilization, normal fertilization rate, stage of embryos transferred, type of embryo transfer, and the number of embryos transferred.

Propensity score matching (PSM) was applied using a multivariable logistic regression model based on age, body mass index (BMI), anti-Müllerian hormone (AMH) level, number of embryos transferred, and stage of embryos (cleavage-stage embryos or blastocysts), and the type of ectopic pregnancy treatment (salpingectomy, salpingostomy, or conservative treatment). Pairs of patients with previous ectopic pregnancy history were derived using 1:1 greedy nearest neighbor matching within a PS score of 0.008. By study design, the patients in the study group were assigned to three subgroups based on hysteroscopic findings: subgroup one consisted of patients whose endometrial pathology was normal, subgroup two who were diagnosed with EP, and subgroup three who were diagnosed with CE.

Protocols of controlled ovarian stimulation and FET

Controlled ovarian hyperstimulation (COH) was performed to maximize follicular response while minimizing the risk of ovarian hyperstimulation syndrome. Even, ovarian stimulation protocols in our reproduction medicine center contain GnRH agonist long protocol, GnRH agonist short protocol, and GnRH antagonist protocol, as described elsewhere. The ovarian stimulation protocols and the daily dose of FSH injection were performed according to female ages, ovarian reserve, and various reactions to ovarian stimulation in previous cycles. Human chorionic gonadotropin (hCG) (hCG; Lizhu Pharmaceutical Trading, China) was administered in patients when three or more follicles reached 16–18 mm or more. For patients at high risk for ovarian hyperstimulation syndrome (OHSS), hCG, in combination with leuprolide acetate, was used to trigger ovulation.

The oocyte retrieval procedure was conducted 36 to 38 hours post-administration of human chorionic gonadotropin (hCG), using transvaginal ultrasonography for guidance. Fertilization was either achieved through conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Subsequently, the embryos were individually cultured in sequential media in micro drops of mineral oil until development stage evaluation on day 3, day 5, or day 6 following oocyte retrieval. The fresh embryo transfer was subsequently executed on day 3, day 5, or day 6 using ultrasound guidance. If the embryos were cryopreserved, the thawed embryo transfer was performed in natural or hormone replacement treatment cycles. The number of transferred embryos or blastocysts was determined in accordance with the Fourth Session of the Committee of Chinese Society of Reproductive Medicine (CSRM) guidelines(19), which recommend a maximum of two embryos per transfer, irrespective of maternal age or the number of transfer cycles. In cases where the patient is young and has multiple high-quality embryos, a single embryo transfer is recommended. Prior to embryo transfer, patients were instructed to maintain bladder filling to optimize ultrasound visualization of the uterine cavity. Under ultrasound guidance, the embryos were gently relocated to a position approximately 1 ~ 1.5 cm from the uterine fundus. After transfer, the catheter was carefully inspected to confirm no embryos remained.

All patients were postoperatively evaluated through a comprehensive follow-up program. A quantitative serum hCG level was determined two weeks post-embryo transfer. A subsequent transvaginal ultrasound examination was scheduled for five weeks post-transfer.

Office hysteroscopy and hysteroscopic surgery

Office hysteroscopy was performed in the proliferative phase and conducted for diagnosis and localization of intracavitary lesions. All hysteroscopy treatments were performed in the operation room of the same two physicians (Tianji Liao and Lijun Lin). Hysteroscopies were performed through the vaginoscopy approach under sedation, utilizing a 2.9-mm, 30-degree-angle hysteroscope with an external sheath of 4.4-mm diameter and offering inflow, outflow, and 5F working channels (Karl Storz, Tuttlinger, Germany). Saline solution (9% concentration) was employed for inflating the uterine cavity (expansion pressure approximating 100 ~ 120 mmHg). The procedure was carried out under a 300-w light source with a high-definition digital camera/xenon bulb (Karl Storz™, Germany). All EP and CE were confirmed histologically. CD138 and CD38 immunohistochemistry (IHC) were conducted. CE diagnostic criteria consisted of ≥ 5 CD138⁺ and CD38⁺cells identified within each high-magnification field (CD138⁺/CD38⁺/HPF, ×400 magnification) within the endometrial stroma. As antibiotic therapy was recommended for CE patients(20), doxycycline (100 mg orally twice a day for 14 days) was administered. A diagnosis of normal endometrium was made when < 5 CD138⁺/CD38⁺/HPF or no plasma cell morphology was observed within the endometrium (21, 22).

Definition of Reproductive Parameters

The clinical pregnancy rate was defined as the number of intrauterine gestations with fetal cardiac activity per IVF-ET cycle. A biochemical pregnancy was defined as a positive hCG level without a gestational sac. Any pregnancy loss after visualization of intrauterine gestation was considered to be a spontaneous miscarriage, and any birth after 24 weeks of gestation was considered to be a live birth. The definition of ectopic pregnancy refers to a pregnancy when the fertilized ovum implants outside the uterine cavity.

Statistical Analyses

Statistical analysis was performed using SPSS software (version 25.0 for Windows; SPSS Inc., Chicago, IL, USA). Normally distributed continuous variables are presented as the mean value ± standard deviation (SD). Nonnormally distributed continuous data are presented as the median and range. Categorical data are described by the number of cases, including numerator/denominator and percentages. A value of p < 0.05 was considered significant. Continuous variables were calculated via dependent-sample t tests or Mann–Whitney U tests as appropriate. Categorical variables were analyzed via the chi-square test or Fisher’s exact test as appropriate. PSM was utilized for sampling at up to 1:1 nearest-neighbor matching with calliper (0.008) to balance the baseline and improve the comparability between groups. The PSM allowed each patient who underwent hysteroscopy to be matched to patients without hysteroscopy after hysteroscopy with similar characteristics, which included age, BMI, number of transferred embryos and stage of transferred embryos (cleavage embryos or blastocyst). By using a previous study comparing the clinical pregnancy rate between women with hysteroscopy in IVF/ICSI-ET (63% versus 41%) without polyps as a reference(23), a total of 714 participants (after PSM) would provide 95% power, assuming a standard deviation of 2 and an alpha of 0.0008.

The clinical characteristics of the study group and control group before and after PSM are shown in Table 1. There were no differences between the two groups in terms of age, BMI, gravidity, or peak estradiol level during the IVF/ICSI cycle. Patient characteristics, such as the total dose and days of recombinant human FSH administration, duration of Gn, endometrial thickness of trigger day, number of embryos transferred, development of stage of the embryo, and transfer embryo cycle between the two groups were also similar after PSM.

Table 1

Baseline characteristics of all patients
				After PSM
	Groups1: Controls (n = 868)	Groups2: Hysteroscopy (n = 455)	P value	Groups1: Controls (n = 357)	Groups2: Hysteroscopy (n = 357)	P value
Age (year)	31.09 ± 0.129	31.18 ± 0.173	0.671	31.08 ± 0.208	31.01 ± 0.191	0.960
BMI (kg/m2)	22.26 ± 0.106	22.04 ± 0.134	0.241	22.25 ± 0.156	22.03 ± 0.150	0.394
Basal FSH(IU/L)	7.02 ± 01.32	6.85 ± 0.165	0.318	6.94 ± 0.181	6.92 ± 0.190	0.929
Basal LH(IU/L)	7.48 ± 0.366	7.57 ± 0.556	0.971	6.80 ± 0.555	7.83 ± 0.665	0.237
AMH	3.80 ± 0.104	3.74 ± 0.146	0.707	3.86 ± 0.162	3.92 ± 0.167	0.905
Duration of infertility (years)	1.82 ± 0.073	1.87 ± 0.106	0.769	1.96 ± 0.112	1.90 ± 0.123	0.639
Total dosage of Gn used (IU)	2460.89 ± 26.708	2345.3 ± 32.336	0.022	2405.52 ± 39.34	2369.5 ± 36.52	0.536
Duration of Gn used (d)	10.26 ± 0.62	10.02 ± 0.75	0.020	10.23 ± 0.088	10.09 ± 0.084	0.256
Peak E2(nmol/l)	3025.80 ± 68.810	2964.40 ± 94.369	0.653	3177.62 ± 110.87	2964.55 ± 100.95	0.086
Number of Oocytes retrieved	11.02 ± 0.215	10.08 ± 0.291	0.549	11.48 ± .0343	10.75 ± 0.314	0.120
Endometrial thickness of trigger day	5.16 ± 0.038	4.99 ± 0.060	0.012	5.15 ± 0.053	5.13 ± 0.066	0.805
ET no. of embryos	1[1,2]	1[1,2]	0.012	1[1,2]	1[1,2]	0.216
Development stage of the embryo			<0.001			0.216
Cleavage embryo	59.67%(518/868)	47.47%(216/455)		60.20%(215/357)	64.70%(231/257)
Blastocyst	40.33(350/868)	52.53%(239/455)		39.80%(142/357)	35.30(126/357)
Treatment of ectopic pregnancy			0.056
Conservative treatment	7.90%(69/868)	6.80%(31/455)		9.80%(35/357)	6.40%(23/357)	0.233
Salpingostomy	34.20%(297/898)	40.90%(186/455)		36.70%(131/357)	36.40%(130/357)
Salpingectomy	57.80%(502/898)	52.30%(238/455)		53.50%(191/357)	57.10%(204/357)

Compared to the controls, the pregnancy outcomes (Table 2) of patients with hysteroscopy showed a slight increase, but with no significant difference in biochemical pregnancy rate, clinical pregnancy rate (66.37 [302/455] vs. 61.75% [536/868], p = 0.097, before PSM, 66.39% [237/357] vs. 60.78% [217/357], p = 0.120, after PSM), Clinical pregnancy rate (58.46% [266/455] vs. 54.61% [474/868], p = 0.180 before PSM, 58.26% [208/357] vs. 53.22% [190/357], p = 0.397 after PSM), the spontaneous miscarriage rate (24.81% [66/266] vs. 18.14% [86/474], p = 0.031 before PSM, 22.12% [46/208] vs. 14.21% [27/190], p = 0.042 after PSM), live birth rate (41.98% [191/455] vs. 43.32% [376/868], p = 0.640 before PSM, 43.14% [154/357] vs. 43.70% [156/357], p = 0.880 after PSM), or ectopic pregnancy rate. Ectopic pregnancy rates were 2.53% [12/474] vs. 3.38% [9/266], p = 0.084 before PSM, 3.68% [7/190] vs. 3.85% [8/208], p = 0.932 after PSM), which consistent with the previous report(24).

Table 2

Reproductive outcomes of all patients
	Before PSM			After PSM
outcomes	Groups1: Controls (n = 868)	Groups2: Hysteroscopy (n = 455)	P value	Groups1: Controls (n = 357)	Groups2: Hysteroscopy (n = 357)	P value
Biochemical pregnancy rate	61.75%(536/868)	66.37% (302/455)	0.097	60.78% (217/357)	66.39% (237/357)	0.120
Clinical pregnancy rate	54.61% (474/868)	58.46% (266/455)	0.180	53.22% (190/357)	58.26% (208/357)	0.397
Spontaneous miscarriage rate	18.14%(86/474)	24.81%(66/266)	0.031	14.21%(27/190)	22.12%(46/208)	0.042
Live birth rate	43.32% (376/868)	41.98%(191/455)	0.640	43.70% (156/357)	43.14% (154/357)	0.880
Ectopic pregnancy rate	2.53% (12/474)	3.38% (9/266)	0.084	3.68% (7/190)	3.85% (8/208)	0.932

A subgroup analysis was conducted on this study group to compare patients who underwent hysteroscopy and exhibited different physiological results. All three subgroups exhibited comparable baseline parameters, except for the endometrial thickness of trigger day (Table 3). The biochemical pregnancy rates, clinical pregnancy rates, and ectopic pregnancy rates of the three subgroups were similar. In contrast, the spontaneous miscarriage rate was higher in the cured CE group than in the normal group (35.39% [24/68] vs. 18.00% [18/100]) and EP group (35.39% [24/68] vs. 10.00% [4/40]). As a result, the live birth rate in the cured CE group was lower than that of the normal group (34.71% [42/121] vs. 45.61% [78/171]) and EP group (34.71% [42/121] vs. 52.31% [34/65]) (Table 4). This difference was still statistically significant after adjusting for confounding variables in logistic regression testing (adjusted OR, Normal group 1.88 [1.102, 3.234], and EP group 2.270 [1.1541, 4.465) (Table 5).

Table 3

Subgroup analysis of hysteroscopy group
Characteristics	Normal group(n = 171)	EP group(n = 65)	CE group (n = 121)	P value
Age (year)	31.03 ± 0.274	31.14 ± 0401	30.92 ± 0.348	0.951
BMI (kg/m2)	21.95 ± 0.205	21.96 ± 0.399	22.19 ± 0.257	0.551
Basal FSH(IU/L)	7.11 ± 0.248	6.80 ± 0.333	6.70 ± 0.403	0.079
Basal LH(IU/L)	7.66 ± 0.836	7.09 ± 1.135	8.44 ± 1.440	0.301
AMH	4.14 ± 0.263	3.47 ± 0.361	3.84 ± 0.260	0.415
Duration of infertility (years)	1.760 ± 0.173	2.10 ± 0.317	2.041 ± 0.207	0.391
Total dosage of Gn used (IU)	2356.32 ± 50.582	2428.12 ± 89.129	2363.76 ± 65.166	0.781
Duration of Gn used (d)	9.99 ± 0123	10.05 ± 0.203	10.29 ± 0.138	0.273
Peak E2(nmol/l)	2908.30 ± 152.375	2848.70 ± 215.214	3091.39 ± 170.177	0.323
Number of Oocytes retrieved	10.17 ± 0.472	11.20 ± 0.808	10.88 ± 0.488	0.731
Endometrial thickness of trigger day	4.88 ± 0.082	5.61 ± 0.160	5.45 ± 0.133	< 0.001
ET no. of embryos	1[1,2]	1[1,2]	1[1,2]
Development stage of the embryo				0.095
Cleavage embryo	56.10% (96/171)	60.00% (29/65)	45.50% (55/121)
Blastocyst	43.90% (75/171)	40.00% (26/65)	54.50% (66/121)
Treatment of ectopic pregnancy				0.291
Conservative treatment	7.60% (13/171)	4.60% (3/65)	5.80% (7/121)
Salpingostomy	34.50% (59/171)	47.70% (31/65)	33.10% (40/121)
Salpingectomy	57.90% (99/171)	47.70% (31/65)	61.20% (74/121)
Baseline characteristics of patients undergoing hysteroscopy before the first embryo transfer, stratified by physiological results.

Table 4

Reproductive outcomes of Subgroups
outcomes	Normal group (n = 171)	EP group (n = 65)	CE group (n = 121)	P value
Biochemical pregnancy rate	65.50% (112/171)	69.23% (45/65)	66.94% (80/121)	0.861
Clinical pregnancy rate	58.48% (100/171)	61.54% (40/65)	57.02% (68/121)	0.778
Spontaneous miscarriage rate	18.00% (18/100)	10.00% (4/40)	35.29% (24/68)	0.003
Live birth rate	45.61% (78/171)	52.31% (34/65)	34.71% (42/121)	0.046
Ectopic pregnancy rate	4.00 (4/100)	5.00% (2/40)	2.94% (2/68)	0.845
Reproductive outcomes of patients undergoing hysteroscopy before the first embryo transfer, stratified by physiological results.

Table 5

Logistic regression analysis of live birth rate in hysteroscopy group
Characteristics	Adjusted OR	95%CI	P Value
Age (year)	0.971	0906-1.041	0.410
BMI (kg/m2)	1.002	0.920–1.091	0.960
Basal FSH(IU/L)	1.090	0.996–1.192	0.060
Basal LH(IU/L)	0.992	0968-1.017	0.547
AMH	0.946	0.854–1.048	0.290
Duration of infertility (years)	0.949	0.854–1.054	0.352
Total dosage of Gn used (IU)	1.000	0.999-1.000	0.262
Duration of Gn used (d)	1.017	0.805–1.285	0.888
Number of Oocytes retrieved	0.993	0.933–1.506	0.814
Endometrial thickness of trigger day	1.195	0.986–1.4448	0.069
ET Cycle	1.146	0.556–2.363	0.712
ET no. of embryo	3.611	1.843–7.077	0.000
Development stage of the embryo	2.262	0.885–5.779	0.088
Treatment of ectopic pregnancy			0.322
Salpingectomy	1
Conservative treatment	0.720	0.440–1.180	0.192
Salpingostomy	1.243	0.504–3.065	0.636
Different of pathological findings			0.024
CE group	1
Normal group	1.888	1.102–3.234	0.021
EP group	2.270	1.154–4.465	0.018
Abbreviations: ET, embryo transfer; CE : chronic endometritis; EP:
Author contribution
Li Xiao: Data Collection, Data analysis, Manuscript writing, Literature Review.
Tianji Liao: Data Collection, Data analysis, Manuscript editing.
Lijun Li: Data Collection.
Wei Huang: Study supervision, Manuscript editing.

Ectopic pregnancy among women of reproductive age is a prevalent and critical health concern. This retrospective study initially demonstrated that the utilization of hysteroscopy had an impact on pregnancy outcomes among patients with a history of ectopic pregnancies. The administration of hysteroscopy benefits patients without CE. To our knowledge, our study represents the first report on the impact of hysteroscopy on clinical reproductive outcomes of IVF treatment for infertile women who had an ectopic pregnancy history.

In this study, the overall ectopic pregnancy rate among patients with previous ectopic pregnancy was consistent with that reported previously (5.1%). After PSM, the hysteroscopy group demonstrated slightly elevated biochemical and clinical pregnancy rates in comparison to the control group; however, these differences did not reach statistical significance. However, it is important to note that the hysteroscopy group experiences a significantly higher rate of spontaneous miscarriage, leading to a similar live birth rate compared to the previously mentioned groups. To deeper into the elevated pregnancy loss observed in the hysteroscopy group, a subgroup analysis revealed that CE played a role in the high loss of pregnancy. In contrast, the normal and EP groups exhibited live birth rates that were higher than those of the CE group.

Our data shows that patients whose endometritis has been confirmed by hysteroscopic means have the highest rate of pregnancy loss. Empirical antibiotic treatment was administered to diminish or eradicate plasmacyte infiltration within the endometrial stroma. Even though all 121 patients with CD138+/HPF ≥ 5 received oral antibiotic treatment, the pregnancy loss rate in this subgroup is the highest(35.39%). This indicated that the current antibiotic strategy might be insufficient to address the issue of endometritis. Antibiotic resistance is a serious global medical problem in the treatment of infectious diseases. A survey investigated the prevalence of antibiotic resistance in CE in a series of 3449 infertile women with a history of RIF with three or more failed IVF-ET cycles, and they found that resistance to first-line 14-day oral doxycycline treatment was found in 21.2% of CE cases (25). It was suggested that, apart from administering doxycycline for 14 days, a combination of levofloxacin lactate and metronidazole for another 14 days may be recommended (20). However, the issue of antibiotic resistance poses a significant global medical challenge in managing infectious diseases, and multi-drug-resistant CE (MDR-CE) is an emerging issue in clinical management. CE was resistant to two courses of combined oral antibiotic treatments (levofloxacin lactate and metronidazole) in 11.0% of cases (20). On the other hand, a growing number of studies demonstrated that antibiotic treatments could enhance the clinical results, but only if a follow-up biopsy confirms the successful eradication of CE (26), however, other research suggests that conducting a second histopathologic examination after initial doxycycline treatment has no significant clinical impact on improving reproductive outcomes in infertile women undergoing ART treatment. Second-look hysteroscopy may be considered as a potential option, even in the absence of conclusive evidence supporting its efficacy in improving reproductive outcomes. An urgent matter is the establishment of universal diagnostic criteria that integrate histopathology, hysteroscopy, and microbiome analysis to address unanswered questions in CE.

The natural course of EP is still not well understood, but it is commonly seen in infertile women. 32% of 1000 women undergoing hysteroscopic evaluation of the uterine cavity prior to IVF were discovered to have, according to a prospective study(27). were identified in 18.21% of 357 patients with previous ectopic pregnancy history. While the exact influence of on fertility remains uncertain, the majority of the studies mentioned above support the notion that pregnant women who have been diagnosed with should have them managed expectantly(28). However, clinical study data are sparse and contradictory. If an endometrial polyp is discovered before FET or before ovarian stimulation for IVF, the patient should be recommended for a hysteroscopy and polypectomy. In cases where a polyp is identified during ovarian stimulation before fresh embryo transfer, specific treatment plans should be implemented based on the quantity of embryos generated, the patient's past reproductive history, and the success rates of each clinic's frozen embryo program(29). In patients with previous ectopic pregnancy history of our study, the live birth rate is significantly higher than in the CE group (52.31% vs. 34.71%), even higher than in the normal group (52.31% vs. 45.61%), which may benefit from the reduced pregnancy loss. This finding may help to support the idea that hysteroscopy administration should occur before embryo transfer in previous ectopic pregnancy history women. The body of evidence supporting the removal of EP is limited, and the best course of treatment must be determined by a carefully planned randomized controlled experiment.

Strengths and Limitations

The primary strength of our study is that the first study to investigate hysteroscopy administration in women with previous ectopic pregnancy history from a single center. However, as with all clinical studies, there were several limitations in our study. The major drawback was the retrospective nature of our study. Even though we matched multiple factors and the groups were generally the same with similar age, BMI, number of transferred embryos, and types of embryos, it is still not possible to entirely rule out the presence of unidentified confounding variables. In addition, the limitation of the present study is the small size of patients with previous ectopic pregnancies. As a result, while the results of this investigation are intriguing, they must be validated through a prospective, case-controlled clinical trial involving an adequately sizable sample. Until now, there has been no prospective investigation of the notably promising effect of hysteroscopy procedures on pregnancy outcomes before embryo transfer. Regarding the CE subgroup, the underlying causes of the elevated spontaneous miscarriage rate and reduced live birth rate remain uncertain: pre-existing microbial invasion, insufficient antibiotic administration, or the potential direct influence of antibiotic use. As for this concern, a second-look hysteroscopy to re-evaluate the symptoms of CE or a subsequent antibiotic administration may be recommended for CE patients, which both need further investigation.

In summary, our findings indicate that the hysteroscopy administration had a positive impact on pregnancy outcomes for patients with a previous ectopic pregnancy history. In addition, even with oral antibiotic treatment, CE findings are inversely proportional to the decline in live births and the rise in pregnancy loss. This proposed nomogram has the potential to provide a new means of routine clinical practice for patients with previous ectopic pregnancies. However, further investigation is needed to determine the necessity of a second-look hysteroscopy and extended antibiotic administration.

Funding

None

Competing interests:

The authors report no financial or commercial conflicts of interest.

Acknowledgements:

The authors thank all the patients included in this study and the staff of the Department of Reproductive Medicine of West China Second University hospital of Sichuan University.

Author contributions

LX wrote the manuscript and reviewed the literature. LX, TJL, and LJL collected and assembled the data. WH designed and conceived the study and amended the manuscript. All of the authors approved the final manuscript.

Conflict of interest

The authors declare that there are no conflicts of interest regarding the publication of this article.

Data availability

The data used in this study will be available upon reasonable request from the corresponding author.

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Reviewers agreed at journal
28 Jul, 2024
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Is it necessary to perform a routine hysteroscopy before first embryo transfer in patients with previous ectopic pregnancy history: A propensity score matching analysis?

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Introduction

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Protocols of controlled ovarian stimulation and FET

Office hysteroscopy and hysteroscopic surgery

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