In this retrospective study, we observed no significant differences in baseline characteristics among the three groups of infertile women. We identified previous adnexal surgery and tuberculosis as potential factors contributing to the development of OP. Additionally, we found that β-hCG levels tended to be higher in OP patients compared to TP patients on the 14th day of ET.
Historically, in 1968, some researchers [13] suggested the existence of intrafollicular and extrafollicular types of OP, with the intrafollicular type receiving less attention in the literature. Subsequently, Dursun et al. [14] stated “ In primary type OP, ovum is fertilized in the peritoneal cavity and then it is implanted into the ovary. Secondary OP develops as a cause of tubal abortion of the embryo and then its implantation to the ovary”. Grimes et al. [15] proposed that normal fertilization could occur in the tube, but implantation in the ovary might result from a conceptus countercurrent. Hallatt et al. [16] noted various ovum release abnormalities leading to intrafollicular fertilization. Despite these insights, the precise mechanism underlying OP development remains unclear due to its rarity. Moreover, early and accurate diagnosis of OP is challenging due to nonspecific clinical presentations, potentially leading to significant intraabdominal bleeding due to the fragility and hypervascularity of ovarian tissue [17]. Therefore, identifying risk factors for OP following ART could aid in prevention and fertility preservation.
Factors such as awkward embryo transfer techniques, manipulation with tissue forceps, patient positioning, and characteristics of culture medium injected into the uterus may contribute to OP occurrence [18]. Blastocyst transfer and ovulation induction cycles may also play roles [19, 20]. During ovulation induction cycles, the high drug levels cause the steroid hormone level increased, the ovaries overstimulated and the ratio of serum estrogen and progestogen changed, then increase the constriction sensitivity of uterine smooth muscle, and move embryos into the tubal by that strong endometrial waves[20]. Oocyte retrieval during ART procedures can cause ovarian surface scars, providing potential sites for embryo implantation [21]. However, in our study, we found no significant differences in ovulation drug dosage, fresh or freeze-thaw cycles, or blastocyst transfer methods. This raises questions about other contributing factors to the increased incidence of OP. Our findings, coupled with existing literature, suggest several potential reasons for this rare event.
The present study underscores a robust association between previous adnexal surgery and OP, echoing the findings proposed by Shan et al. [11]. Their work suggests that such surgeries could alter the inherent uterine structure, potentially leading to ovarian inflammation, ovulation barriers, and the implantation of fertilized eggs within the ovary. Adnexal surgeries commonly encompass unilateral or bilateral salpingectomy or ovariectomy, often necessitated by conditions like hydrosalpinx, fallopian tube obstruction, ovarian cysts, ruptured corpus luteum, and even rare instances of pregnancy. Multiple studies have highlighted the adverse prognostic implications of tubal factor infertility, particularly in women undergoing IVF-ET [22]. Pelvic adhesions and PID resulting from various adnexal surgeries can alter the ovarian surface and disrupt ovum release, potentially facilitating ovarian implantation. These findings underscore the etiological significance of prior adnexal surgery in OP and suggest that the indications for such surgeries may contribute to OP incidence.
Furthermore, our investigation unveils a potential association between tuberculosis and the incidence of OP. While tuberculosis primarily affects organs such as the fallopian tubes, uterine endometrium, and ovaries, its impact on the female reproductive system varies widely [23]. The tubal ampulla presents the earliest change, the fimbrial processes turn into swollen later. The pathological changes of tuberculosis endometritis include endometrial ulceration, caseous necrosis, haemorrhage, and adhesions may occur between ovaries and adjacent pelvic organs leading to adnexal mass[24]. Genital tuberculosis can lead to infertility[25], menstrual irregularities, ovarian cysts, and PID, with infertility being a predominant symptom, especially in developing nations [26]. Notably, genital tuberculosis's role in the genesis of EP has been documented [27], although the precise mechanisms underlying ovarian implantation remain elusive. The rising incidence of genital tuberculosis, fueled by factors such as increasing multi-drug resistance in Mycobacterium tuberculosis, heightened population mobility, and lax tuberculosis management among females, suggests a growing high-risk population for OP. However, our findings are constrained by the single-hospital setting and the low incidence of the disease, necessitating validation through larger-scale studies.
In our current investigation, we observe elevated β-hCG levels in OP patients compared to TP patients on the 14th day post-embryo transfer, consistent with prior research [12]. Goksedef et al. [28] have noted that ruptured EP often present with elevated β-hCG levels, potentially due to increased vascularity of ovarian tissue facilitating embryonic development. This observation hints at a potentially poorer prognosis for OP patients, given the association between high β-hCG levels and ovarian rupture. It has also been reported that OP can have negative HCG tests [29]. Therefore, there is a risk of both underdiagnosis and overdiagnosis of OP due to cognitive biases [30].