Reeta Singh¹, Ruma Sarkar², Vani Aditya³, Babita V Agarwal^4*

^1,2Associate Professor, ³Professor. ⁴Assistant Professor, Department of Obstetrics and Gynaecology, B.R.D. Medical College, Gorakhpur, Uttar Pradesh, INDIA.

Email: vaswani.babita@gmail.com

Table 1: Age of patients of EP and IUP

Table 2: Full term deliveries in enrolled patient

Table 3: Association of previous EP and infertility with EP in cases and controls

Table 4: History of spontaneous abortion, puerperal infection, and postabortion infection among the enrolled patients

Table 5: Comparison of appendicectomy, tubal corrective surgery, C-section, and adnexal surgery among enrolled patients

Table 6: History of genital and extragenital TB among the enrolled patients

Table 7: History of IUCD, tubectomy, and current use of LNG EC among enrolled patients

Among both groups, we found that previous history of ≥1spontaneous abortion is associated with significantly high risk of EP [odds ratio (OR) = 6.879, 95% confidence interval (CI) = 0.3760–125.9]. Previous history of puerperal infection and post abortion infections also shows association with EP (OR = 4.064, 95% CI = 0.4181–35.50 and OR = 4.053, 95% CI = 1.263–13.00 respectively).We took the history of PID, but almost every patient had a history suggestive of PID at least once in their life- time. So, we specified the history to only post abortion and puerperal period. Table 5 compares the surgical history of all enrolled patients of EP and IUP as risk factor assessment. We compared the history of appendectomy, tubal corrective surgeries, C-section, and adnexal surgery among both groups with EP and IUP. We found that previous history of tubal corrective surgery was present in 3 out of 144 patients of EP, and none of enrolled patients of IUP had history of tubal corrective surgeries. Among these three tubal corrective surgeries, two were recanalization and one was peritubal adhesiolysis. This finding shows strong association between tubal corrective surgery and EP (OR = 9.919, 95% CI = 0.5080–193.7). We also found association between history of appendectomy, C-section, adnexal surgery, and occurrence of EP (appendectomy: OR = 1.394, 95% CI = 0.1940–10.02, C-section: OR = 1.446, 95% CI = 0.840–2.486, adnexal surgery: OR = 1.876, 95% CI = 0.4133–8.578). Adnexal surgery included cystectomy and ovarian drilling for polycystic ovarian disease. Table 6 compares history of genital TB and extra genital TB among the patients of EP and IUP. All the patients had received antitubercular treatment (ATT). A total of 3 out of 15 patients were still taking ATT. We found increased risk of EP in patients of genital and extragenital TB (OR = 2.803, 95% CI = 0.2516–31.23 and OR = 4.378, 95% CI =1.163–16.47 respectively). In Table 7, we can see a strong association between failed tubectomy and EP (OR 2.829, 95% CI = 0.5108– 15.66). We also found association between EP and use of LNG EC in current cycle (OR = 1.993, 95% CI = 0.6194–6.411). Four out of seven women who had EP and used LNG EC in current cycle took LNG EC ≥ 2 times in same cycle and did not use any other contraception. We did not find any association between EP and past and current use of IUD.

DISCUSSION

In the current study, we found the incidence of EP to be 23.67/1,000 ANC admissions in our institution. Patel et al.⁶ found mean rate of EP as 11.41/1,000 births. Incidence of EP was found to be 3.99/1,000 deliveries by Mufti et al.⁷ and 5.6/1,000 deliveries by Shetty and Shetty⁸ We found that the risk of EP increases in women over 30 years of age. Similarly, in a case–control study by Karaer et al..⁹ they found that an increase in rate of EP coincides with an increase in the age of women before reaching age 40. Bouyer et al¹⁰ also reported a significant relation between age and EP. The mean age of the cases was significantly higher than that of the controls (30.3 ± 5 vs. 27.1 ± 5.3) as indicated by Moini et al.¹¹ The role of age in the incidence of EP has been suggested by researchers. However, studies have produced conflicting results in this respect. The peak age of incidence was 26 to 30 years in Majhi et al.¹² Gupta et al.¹³ found a maximum 72.5% cases were in the age group of 21 to 30 years. The precise physiological impact of advanced maternal age on EP risk is unclear.10 It has been reported that the age-related changes in tubal function may delay ovum transport, leading to tubal implantation.  However, these hypotheses remain to be tested. Furthermore, Coste et al.¹⁴ found that this association refers to the probability of exposure to most risk factors, which increase with age.  Conversely, another study by Pulkkinen and Talo¹⁵ has suggested that age plays a more important role as compared with other risk factors. We observed that women with ≥2 full-term deliveries are at increased risk of occurrence of EP (p = < 0.05). Similarly Cheng Li et al.¹⁶ showed association of EP with parity (once: OR = 1.14, 95% CI: 1.02–1.30; more than twice: OR = 1.58, 95% CI: 1.27–1.96). The highest incidence of EP was found among women who were Para 2, 32.9% by Pal et al.¹⁷ Parashi et al.¹⁸ found that the case and control groups had similar parity. Majhi et al.¹²found that most sufferers were primi. So, correlation with parity and EP is not consistent. As we can see in Table 3, traditional risk factor like history of previous EP was not present in a single patient of EP, but was present in 5 (2.5%) cases of IUP. Malathi et al.¹⁹ found history of EP in 7.8% of EP cases and Shetty and Shetty⁸ found it in 3.2% cases of EP. Barnhart et al.²⁰ found that among all the possible risk factors of EP, the strongest evidence is for an association between previous EP and subsequent EP. As traditional risk factors, history of infertility was found as a major risk factor. Same was found in a study by Mufti et al.⁷ and Mishra²¹ – 8.77 and 9.67% respectively. Previous ≥1 spontaneous abortion is associated with six times increased risk of EP. Several other studies, e.g., Moini et al.²¹ and Bouyer et al.²² and our study have shown the association of prior spontaneous abortion with increased risk of EP. With regard to the available evidence, the cause of this relationship is most likely due to infection as shown in Bouyer et al.^10,23 hormonal imbalance as shown by Bouyer et al.,¹⁰ Doyle et al.,²³ Fernandez et al.²³; or immunologic factors as shown by Bouyer et al.10 History of post abortion and puerperal infection is associated with increased risk of EP. This association appears to be due to PID after abortion and delivery. The PID leads to chronic pelvic pain, pain during intercourse, infertility, and a higher risk of EP. Post abortion antibiotic prophylaxis is advised for both induced and spontaneous abortion as found in Montgomery et al.²⁵ The IgG antibody test for Chlamydia trachomatis was not available in our institution. Intraoperative findings of EP were available, but could not be compared with that of IUP. So, we were solely dependent on clinical history of PID. Adnexal surgeries, C-section, appendicectomy, and tubal surgeries were found to be increased risks for EP. Tubal corrective surgeries performed were recanalization in two cases and peritubal adhesiolysis in one case. It has been reported that previous tubal surgery is a major risk factor for EP, with an estimated OR of 4.7 (2.4–9.5) according to a metaanalysis by Ankum et al.²⁶ There was no statistically significant relation found between EP and prior tubal surgery in Parashi et al.¹⁸ It is uncertain whether the increased risk is arising from a surgical procedure or from the underlying problem. In Cheng Li et al.,¹⁶ previous adnexal surgery and previous appendicectomy were found to be associated with increased risk. This increased risk is most probably due to formation of adhesion in adenexa, which impairs tubal function. In the current study, we found the increased risk of EP in patients of genital and extragenital TB (OR = 2.803, 95% CI = 0.2516–31.23 and OR = 4.378, 95% CI =1.163–16.47 respectively). In Sharma et al.,²⁷ genital TB was responsible for 13.2% of all cases of EP. We in our study sent the samples of salpingectomy in 132 cases of ruptured EP for histopathological examination, acid fast staining, and DNA polymerase chain reaction (PCR) of Mycobacterium TB. We also performed Monteux test on the cases, but we could not do the same in controls. So, we could not compare the data between cases and controls. Contraceptive failure is considered to be an important factor associated with the increased incidence of EP. Due to the national family planning policy and religious and social practices of people in this region, there may be a difference in the contraception preferences. All methods of contraception can effectively reduce the number of IUPs and EPs. However, from our study, when pregnancies occur as a result of contraceptive failure, the risk of EP is significantly increased in women, who become pregnant after tubal sterilization and LNG EC. In our study, we saw that if pregnancy occurs in women of tubal ligation, there is 2.829 times increased risk of EP. Similar finding was found in study of Patel et al.⁶ and Mufti et al.⁷ We did not find any association of past and current user of IUD and EP. The LNG EC use in current cycle shows a 1.993 times increased risk of occurrence of EP as the same was found in the study by Cheng Li¹⁶ and Zhang et al.²⁸ Previous studies indicated that progesterone and its analog, LNG, could effectively inhibit human tubal activities as shown by Wanggren et al.²⁹ and Zhao et al.,³⁰ which have been considered as the main cause of impaired embryotubal retention and implantation, as documented in Shaw et al.³¹

CONCLUSION

Motherhood is the identity of women in India. We can see that the two extremes of her motherhood – infertility and high parity – both are responsible for this dreaded outcome of pregnancy. Factors contributing for the causation of EP in both conditions are different. In cases of high parity, post abortion infection, puerperal infection, increasing age of mother, and contraception exposures appear to be main contributing factor for EP. Tuberculosis has come out as a major risk factor of EP in our study. Being a developing country, we are still fighting with Mycobacterium TB, which is a silent moth of the human organ system. Though new, finer diagnostic tools of detection of TB are increasingly available in the form of bacterial cultures and PCR-based diagnostics, suspicion by clinicians remains the main tool for diagnosis of the condition. Hence, doctors need to be properly trained to become more conscious of TB. Active TB infection, especially in adolescent period, should be taken care of aggressively. By identifying risk factors being amenable to modification, such as post abortion and puerperal infection, the effective risk-reduction strategies should be devised and that helps in safe motherhood. Guidelines for adnexal surgeries should be targeted for reduction of postoperative adhesion. Intraoperative and postoperative precautions should be taken to reduce adhesion. Over-the-counter availability of LNG EC should be stopped because irrational and inappropriate use of LNC EC has come out as an important emerging risk factor for EP. Long-time known risk factors like infertility, parity, and PID are inherent aspects of womanhood. We should concentrate on modifiable risk factors like pelvic surgeries, contraception, and TB for the prevention of EP.

ACKNOWLEDGMENT

We express our sincere thanks and gratitude to our assistant, associate professors and professors of obstetrics and gynaecology department. We are thankful to our postgraduate students and paramedical staff.

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