Role of Diagnostic Hysteroscopy in Cases with Unexplained Infertility

DISCUSSION

After a year of unprotected regular intercourse, infertility is described as the inability to conceive. It affects about ten to fifteen percent of marriages. The most common causes of infertility are male factor (30–40%), uterine factor (15–20%), ovulatory disorders (30–40%), and tuboperitoneal illness (40–50%). Hysteroscopy is a great diagnostic tool for detecting concealed pathology in people who have no obvious symptoms. Even after a normal HSG, laparoscopy can reveal the existence of peritubal adhesions, periadnexal adhesions, tubal pathology, and endometriosis in 35–68% of patients. ¹⁵.

Infertility is a problem that many physicians encounter on a daily basis. Only a few people are able to conceive with only diagnostic methods; others, despite extensive investigations and treatment, are unable to conceive. Cervical, uterine, tubal, and ovulatory variables are all evaluated in the early stages of female infertility. Historically, hysterosalpingography was used to assess the uterine cavity (HSG). Nevertheless, for direct visualization of the cavity of the uterus, hysteroscopy is becoming more popular, and many researchers believe it is preferable to HSG ¹⁴.

Unexplained infertility affects about 15% of people who are experiencing infertility. The diagnosis tests to be conducted, their predictive usefulness, and the normalcy criteria are not agreed upon by infertility specialists. The basic diagnostics for diagnosing unexplained infertility are reported to be levels of serum progesterone for identifying ovulation, HSG and/or laparoscopic for tubal patency, and analysis of semen ¹⁶.

In contrast to the other indirect and purely diagnostic techniques, such as transvaginal sonography (TVS), hysterosalpingography (HSG), and saline infusion/gel instillation sonography (SIS/GIS), hysteroscopy is currently the gold standard approach for uterine factor assessment since it allows direct visualization of the cavity of the uterus and its related clinical diseases, and also therapy of any diagnosed aberration. Nonetheless, there is no agreement on the effectiveness and efficiency of hysteroscopy as a standard treatment in the infertility work-up or on its effectiveness and efficiency in enhancing infertile couples' prognosis ¹⁷.

Because the usefulness of hysteroscopy in enhancing reproductive outcome has not been shown, the NICE recommendations on fertility evaluation and treatment advise that, unless clinically warranted, women ought not to be provided hysteroscopy as a portion of the first inquiry ¹⁸.

Hysteroscopy involves a rapid, painless, and well-tolerated procedure that allows direct visibility of the cervical canal and cavity of the uterus, allowing any abnormality's form and vascular patterns to be observed ¹⁹.

It is a first-line diagnostic technique for uterine anomalies in individuals who have abnormal uterine hemorrhage and/or infertility because it can be done in the office. Furthermore, the hysteroscopic method allows for the collection of endometrial/myometrial samples under visual supervision ²⁰.

The main goal of this research was to assess the role of hysteroscopy in the detection of undiagnosed uterine abnormalities in cases with unexplained infertility.

The study was a cross sectional study. The research was conducted at the endoscopy unit in Al-Hussein and Sayed Galal hospitals on 100 women with unexplained infertility at a period of 6 months from January to June 2021.

The following were the study's major findings:

Regarding the demographic data of the studied group, we revealed that patients’ mean (range) age was 28.63 ± 5.12 (20 – 40) years with mean BMI 27.54 ± 3.65 kg/m2. The patients were mostly from rural areas. And the infertility mean duration was 6.74 ± 4.35(1 – 14) years. Majority of the patients were primary type of infertility (68%).

In a study by Gammo 21, the pregnancy outcomes following hysteroscopy in patients experiencing unexplained infertility were investigated. They enrolled 200 infertile women who had been identified with unexplained infertility earlier. They were divided into 2 groups: A. the study group of 100 infertile females who had been shortlisted for the hysteroscopic surgery under study with a mean age 25±5 years and a mean BMI 24±3.6 and B. the control group of 100 females having unexplained infertility who were followed up on but did not get the recommended hysteroscopic procedure with a mean age 26±3 years and a mean BMI 23±1.7. Thy also reported that the mean infertility duration of the cases and control groups were 2 + 2.1 and 2.1 + 1.3 years respectively and the majority of the patients of cases and control groups were primary type of infertility (70% and 75% respectively).

As well, the study by Al-Bromboly et al. ¹⁵ investigated the role of hysterolaparoscopy in the assessment and treatment of infertility in women. They divided the studied groups into primary and secondary types of infertility. They found no significant differences between the studied groups regarding age, they also, revealed that there were 42.7% of primary infertility and 59.5% of secondary infertility cases.

An observational cross‑sectional study by Gad et al., 2019 investigated the role of hysteroscopy and laparoscopy in the assessment of unexplained infertility in 200 women aged 20–40 years old, of whom 116 (58%) experienced  primary infertility and 84 (42%) experienced secondary infertility.

The study by Sharma et al., 2017 performed a retrospective study of hysterolaparoscopy results of unexplained infertility cases in a tertiary care hospital. The study included 130 patients, with 82 patients (63.07%) having primary infertility and 48 patients (36.92%) having secondary infertility. The majority the patients (80, 61.5%) were between the ages of 26 and 30. Ten cases (7.7%) were between the ages of 20 and 25, 32 (24.6%) were between the ages of 31 and 35, and eight (6.1%) were between the ages of 36 and 40.

In addition, Makled et al. ¹⁴ evaluated the effects of hysteroscopy and endometrium biopsy in women who were infertile for no apparent reason. The study included 100 women with infertility. Participants ranged in age from 18 to 45 years old, with an average age of 30.77 4.82 years. With a range of 18.5–33.5 kg/m2, the average BMI was 27.7 3.51 kg/m2. Parity was 0.88 0.38 on average (range 0–2).  Forty women (40%) experienced primary infertility, while 60 women experienced subsequent infertility. Infertility lasted anywhere from two to ten years.

Regarding Hysteroscopy findings among studied patients, the present results revealed that abnormality hysteroscopy was found in 89% of the studied patients.

Our study was supported by the findings by Al-Bromboly, et al. ¹⁵ as they revealed that abnormality hysteroscopy was found in 72.5 % and 71.5 of the primary and secondary type of infertility patients respectively.

Also, the study by Makled et al. ¹⁴ reported that no hysteroscopic abnormality was discovered in 14% of the women who had unexplained infertility.

In contrast with our findings the study by Gammo ²¹ they found that 70 (70%) of the women with unexplained infertility have normal hysteroscopic findings.

As well the study by Gad et al. ¹⁹ revealed that 64.3% of the women with unexplained infertility have normal hysteroscopic findings, with 58.3% and 72.0% of the primary and secondary type of infertility patients respectively.

Also, the study by Sharma et al. ²⁰ reported that 77.7% of the women with unexplained infertility have normal hysteroscopic findings.

Also, in disagreement with our findings, the study by Zargar et al. ²² reported that 33 cases (61.2%) showed normal hysteroscopic results and 21 cases (38.8%) showed abnormal hysteroscopic results out of 54 women experiencing unexplained infertility.

Furthermore, Kabadi & Harsha ²³ reported 52% abnormal laparoscopic findings and 31% abnormal hysteroscopy, Ramesh & Kurkuri ²⁴ reported higher incidence of approximately 75% abnormal hysterolaparoscopy findings, Vaid et al., ²⁵ reported 62% abnormal laparoscopy and 32% abnormal hysteroscopy findings, and Nigam and colleagues found similar laparoscopic abnormalities and less rate of hysteroscopic ones (13%). Nayak et al. ²⁶ found also lower results of approximately 33% abnormal laparoscopy and 20% abnormal hysteroscopy findings.

Regarding abnormal hysteroscopy findings among studied patients, we found that the majority of women have endometrial polyp (30%), then Hyperplastic (14%), Endometritis (13%), Submucous myoma (9%), Intrauterine Synechia (8%), Cervical polyp (4%), Septum (3%), Cervicitis (2%), Arcuate uterus (2%), Unicornuate uterus (2%), Bicornuate uterus (1%) and Cervical stenosis (1%).

The study by Gammo, ²¹ revealed the following anomalies: atypical polypoid adenomyoma of the endometrial in three patients (3%), and intrauterine adhesion (IUA) synechiae in three patients (3% of all hysteroscopies). Uterus bicornis was found in a patient (1% of all hysteroscopies), submucousmyoma was found in 3 cases (3% of all hysteroscopies), and in 20 patients, there were endometrial polyps (20% of all hysteroscopies).

And also, the study by Al-Bromboly, et al. ¹⁵ reported that showed that the commonest reported hysteroscopic abnormality in cases of primary infertility was intrauterine septum, and the commonest reported hysteroscopic abnormality in cases of secondary infertility was intrauterine synechia.

In addition, the study by Gad et al. ¹⁹ reported that among the abnormal laparoscopic findings, pelvic adhesions and endometriosis were the most noted (41 and 30%, respectively).

Also, the study by Sharma et al., 2017 reported that hysteroscopic anomalies showed myoma and polyp in 10 (7.7%) of the women with unexplained infertility, as well as synechiae in 5 (3.8%) of the women.

Makled et al. ¹⁴ reported also that 7 (7%) had intrauterine synechiae, 6 (6%) had submucous myomas, 15 (15%) had endometrial hyperplasia, 14 (14%) had endometritis, and 31 (31%) patients had endometrial polyps (total 73 patients = endometrial anomalies group); 6 (7%) had cervical stenosis (no anomalies group); and 7 (7%) had congenital uterine anomalies (uterine anomalies group).

Regarding the diagnosis role of hysteroscopy among the studied patients, we found that 87% have Abnormal TVS and 89% have abnormal hysteroscopy, there was highly significant difference between the abnormal and normal Hysteroscopy regarding the TVS findings.

Using the area under the ROC curve, we found that hysteroscopy was significant with a sensitivity of 97.8% and specificity of 100%, a PPV of 100%, an NPV of 84.6%, and an accuracy of 98%.

Our results were supported by the findings by Garuti et al. ²⁷ who reported that hysteroscopy has a good diagnostic accuracy for the detection of endometrial polyps (95.3 percent sensitivity, 95.4 percent specificity, 98.9 percent NPV, and 81.7 percent PPV).

While Makled et al. ¹⁴ reported that in 31 (31%) of the infertile individuals, diagnostic hysteroscopy revealed endometrial polyps, only 18 (18%) of those patients were appropriately detected by TVS. Seven of the individuals that were overlooked exhibited hyperplasia, while the other six had no abnormalities. The NPV was 84.1 percent, indicating that endometrial polyps were discovered by hysteroscopy in 15.9% of people who had TVS-negative results. The PPV, on the other hand, was 100 percent, meaning that all patients who had endometrial polyps by TVS also had endometrial polyps by hysteroscopy. As a result, while TVS is an excellent positive testing, it cannot be employed on its own to exclude out endometrial polyps.

Makled et al. ¹⁴ also reported that the NPV was 71.1 percent, indicating that 28.9% of individuals who'd been endometrial negative via hysteroscopy had endometrial polyps. The PPV, on the other hand, was 100%, meaning that all individuals identified with endometrial polyps via EB had an endometrial polyp found via hysteroscopy. The NPV was 100 percent, which means that none of the people who had a negative hysteroscopic result had endometrial hyperplasia when histological examinations were done. Furthermore, the PPV was 93.3 percent (meaning that every woman with hysteroscope-based hyperplasia has a 74.2 percent chance of developing endometrial hyperplasia via EB). The NPV was 98.8%, meaning that EB detected endometritis in 1.2 percent of hysteroscopy-negative individuals. The PPV, on the other hand, was 100 percent (That is, all women who had endometritis via hysteroscopy also had endometritis via EB).

Hauge et al. ²⁸ found that the results of hysteroscopy and TVS were identical in 90.9 percent of patients. Oliveira et al. ²⁹ discovered a link between IVF and ET failure and previously undetected intrauterine anomalies.

Our findings were backed up by those of Draz et al. ³⁰ who found that hysteroscopy was more sensitive (100 versus 85%), had the same specificity (100 versus 100%), and was more accurate (100 versus 94%) than saline infusion sonography. During the evaluation of individuals with unexplained infertility, hysteroscopy had a better predictive value (100 versus 100 percent PPV, 100 versus 90 percent NPV) than saline infusion sonography (100 vs. 90 percent negative predictive value).

In contrast to our findings, Zargar et al. ²² found that hysterographic and sonographic sensitivities were 48.9% and 48 percent, respectively, while false negative rates were 51.1 percent and 52 percent. As a result, sonography and hysterography were insufficient for evaluating the uterine cavity.

Furthermore, Preutthipan & Linasmita ³¹ conducted a prospective comparison research of hysterosalpingography and hysteroscopy in the identification of intrauterine disease in infertile women and found that HSG had a sensitivity of 98.0 percent but only 34.6 percent specificity. In this study, HSG had a high sensitivity but a poor specificity rate when it came to detecting intrauterine abnormalities. As a result, while HSG is a helpful screening test for intrauterine lesions because it shows the filling defects, the filling defects obtained by HSG are non-specific. Only hysteroscopy was able to accurately reveal the nature of the intrauterine filling abnormalities. When an HSG reveals any lesions, hysteroscopy is recommended to confirm the lesions' location and extent.

Failure to complete the surgery, cervical laceration, uterine perforation, infection, haemorrhage, anesthesia-related issues, and a very rare syndrome called carbon dioxide embolism are all possible risks of diagnostic hysteroscopy. There were no procedure failures or significant complications among our 336 patients 31 in this study. Three RCTs revealed no problems ^34,35,36; four trials quantified adverse events ^32,33.

CONCLUSION

Before a final diagnosis of unexplained infertility, a hysteroscopy must be scheduled as one of the standard measures in the reproductive work-up programme. Because of the significant enhancement in pregnancy outcomes after the hysteroscopic operation, this method is deemed not only an optimal gold standard for finding numerous intrauterine problems that are undetected with other standard techniques, but it also supports the previously mentioned recommendation. In addition, it is suggested that future study be conducted to back up this statement.