Association between ovarian maldescent and infertility: a prospective cohort study.

We conducted a single-center, prospective cohort study involving female patients with infertility issues who were admitted to the reproductive endocrinology ward between January 2018 and November 2023. The present study was approved by the Ethics Committee of Obstetrics and Gynecology Hospital of Fudan University and performed according to the Declaration of Helsinki. Written informed consent were obtained from all participants, who also consented to the publication of anonymized data. The experimental group consisted of women diagnosed with ovarian maldescent (unilateral or bilateral) on the basis of intraoperative findings. The control group included women with infertility due to tubal, ovarian, uterine, or other factors who were randomly matched at a 1:2 ratio. After screening and providing informed consent, eligible participants were invited to join the study. The general characteristics of both groups, including maternal and paternal age, infertility duration, body mass index (BMI), serum anti-Müllerian hormone (AMH) levels, reproductive history, and the etiology of infertility (tubal, ovulatory, uterine, and male factors, etc.) were compared between the two groups. We subsequently conducted a one-year follow-up on the pregnancy outcomes of both groups to investigate the associations between ovarian maldescent and infertility. The analysis included the methods of conception (non-IVF, encompassing spontaneous ovulation, ovarian stimulation, or IVF) and the DOP for conception. This study will enroll women who meet either of the following criteria: (1) infertility for ≥ 1 year with unsuccessful conception despite unprotected intercourse, or (2) abnormal hysterosalpingography (HSG) findings (tubal occlusion, hydrosalpinx, or uterine cavity abnormalities) regardless of infertility duration. All participants must provide informed consent for diagnostic/therapeutic laparoscopy following complete infertility evaluation. The following patients were excluded from the study: (a) those who underwent myomectomy during the procedure so that they required a specified period of postoperative contraception; (b) patients who underwent ovarian surgery, where ovarian function may have been affected, to the extent that recovery would take a significant period of time; (c) individuals with severe uterine malformations that cannot be corrected through surgery or that require an extended recovery period; (d) patients who presented with severe hydrosalpinxand tubal obstruction during surgery, with uncertain outcomes regarding the improvement of fallopian tube function following salpingostomy; (e) those who had previously undergone salpingectomy or who were undergoing the procedure during this surgery. The characteristics of the study participants were summarized. Continuous variables are expressed as the means (standard deviations) and compared using Student’s t test. For non-normally distributed variables, including male age, AMH level, and the duration of infertility, the Mann‒Whitney U test was employed. Categorical variables are presented as percentages and were analysed by the chi-square test. The DOP for conception in both the control and ovarian maldescent groups was estimated by the Kaplan‒Meier method. Multivariate analyses were conducted using the Cox proportional hazards model to assess the simultaneous effects of confounding variables. All the statistical analyses were performed via SPSS Statistics version 24 (IBM, Chicago, USA), with a two-side P -value < 0.05 considered statistically significant .

A total of 2,306 surgeries were performed in the reproductive endocrinology ward between January 2018 and November 2023. On the basis of the established inclusion and exclusion criteria, 22 patients were identified as having unilateral or bilateral ovarian maldescent during surgery. One patient from this group, who did not intend to pursue pregnancy postoperatively, was subsequently excluded. Additionally, 44 patients without ovarian maldescent were randomly selected to form a control group at a 1:2 matching ratio. During follow-up, two patients from the control group discontinued attempts to conceive, one due to hyperthyroidism and the other due to personal reasons, leading to their exclusion. As a result, 42 patients remained in the control group. In the experimental group, six patients presented unilateral ovarian maldescent with normal morphology and positioning on the contralateral side, whereas fifteen patients presented bilateral ovarian maldescent. The basic characteristics of the two groups were retrospectively analysed (Table  1 ). No significant differences were observed between the groups in terms of body mass index (BMI), duration of infertility, reproductive history, or male age. However, the females in the experimental group were slightly younger than those in the control group (27.9 ± 3.8 vs. 29.8 ± 3.3 years, P  = 0.039). Additionally, serum anti-Müllerian hormone (AMH) levels, measured as part of routine fertility testing in all patients, were within the normal range for ovarian reserve in both groups (4.5 ± 2.9 vs. 6.2 ± 2.8, P  = 0.003). The distribution of infertility factors (tubal, ovulatory, uterine, or male) was comparable between groups . Given that the patients in the experimental group had unilateral or bilateral ovarian maldescent, we further subdivided them accordingly. A reanalysis of the basic characteristics and clinical data mentioned above revealed no significant differences between the two subgroups. Table 1 General characteristics of infertile women General characteristics Control group ( n  = 42) Experimental group ( n  = 21) P Experimental group P Unilateral (n=6) Bilateral (n=15) Age, years 29.8 ± 3.3 27.9 ± 3.8 0.039 28.0 ± 3.9 27.8 ± 3.9 0.916 Male age, years 30.7 ± 2.7 30.0 ± 2.2 0.330 30.0 ± 1.8 29.7 ± 2.4 0.629 Body-mass index, kg/m 2 22.5 ± 2.9 22.8 ± 3.4 0.666 22.1 ± 3.4 23.1 ± 3.5 0.518 AMH, ng/ml 4.5 ± 2.9 6.2 ± 2.8 0.003 7.8 ± 3.4 5.6 ± 2.3 0.139 Duration of infertility, years 2.0 ± 1.4 2.3 ± 1.4 0.406 2.2 ± 1.5 2.3 ± 1.4 0.777 Nulliparous (%) 18 (42.9) 5 (23.8) 0.139 0 (0.0) 5 (33.3) 0.262 Cause of infertility Tubal factors (%)  PID 26 (61.9) 12 (57.1) 0.716 4 (66.7) 8 (53.3) 0.659  Endometriosis 17 (40.5) 7 (33.3) 0.582 1 (16.7) 6 (40.0) 0.613  Others 29 (69.0) 12 (57.1) 0.350 3 (50.0) 9 (60.0) 1.000 Ovary factors (%)  PCOS 5 (11.9) 6 (28.6) 0.157 2 (33.3) 4 (26.7) 1.000  Others 3 (7.1) 4 (19.0) 0.209 2 (33.3) 2 (13.3) 0.544 Uterine factors (%)  Mullerian anomalies 1 (2.4) 2 (9.5) 0.256 0 (0.0) 2 (13.3) 1.000  Others 19 (45.2) 12 (57.1) 0.373 3 (50.0) 9 (60.0) 1.000 Male factors (%) 4 (9.5) 3 (14.3) 0.677 1 (16.7) 2 (13.3) 1.000 Plus–minus values are means ± SD AMH Anti-Müllerian hormone, PID Pelvic inflammatory disease, PCOS Polycystic ovarian syndrome a : Mesosalpinx cysts, accessory fallopian tube ostium, accessory fallopian tube fimbria and other structural factors b : Hyperprolactinemia, and thyroid-related disorders and so on c : Adenomyosis, leiomyoma, endometrial polyps, cervicitis, uterine synechiae, and endometritis General characteristics of infertile women Plus–minus values are means ± SD AMH Anti-Müllerian hormone, PID Pelvic inflammatory disease, PCOS Polycystic ovarian syndrome a : Mesosalpinx cysts, accessory fallopian tube ostium, accessory fallopian tube fimbria and other structural factors b : Hyperprolactinemia, and thyroid-related disorders and so on c : Adenomyosis, leiomyoma, endometrial polyps, cervicitis, uterine synechiae, and endometritis Fisher’s exact test revealed that 9 women in the ovarian maldescent group achieved pregnancy through spontaneous or stimulated ovulation, whereas 34 women in the control group achieved pregnancy (Table  2 ). Consequently, the non-IVF pregnancy rate in the control group was significantly higher (56.3% vs. 91.9%, P  = 0.005). Among women who pursued IVF, the conception rates were comparable between the two groups(60% vs. 60%, P  = 1.0). Furthermore, no statistically significant difference in pregnancy rates was observed between women with unilateral and those with bilateral ovarian maldescent (Supplemental Table 1). One case of ectopic pregnancy with abortion and two cases of pregnancy loss were observed in ovarian maldescent group, whereas the control group had one pregnancy loss and no ectopic pregnancies. Table 2 Pregnancy outcomes in the experimental group and the control group Group Non-IVF IVF Total Pregnant Non-pregnant Pregnant Non-pregnant Control group 34 3 3 2 42 Experimental group 9 7 3 2 21 P 0.005 1.0 Pregnancy outcomes in the experimental group and the control group The DOP for conception through non-IVF methods was analysed using the Mann‒Whitney U test, which revealed a significantly longer preparation time in women with ovarian maldescent than in controls ( P  = 0.001, Supplemental Fig. 1a). Subsequent Kaplan‒Meier survival analysis demonstrated that the median DOP for conception was seven months for women with ovarian maldescent, whereas it was three months for the control group (HR = 2.927, 95% CI: 1.390, 6.165; P  = 0.005; Fig.  1 ). However, no significant differences in preparation time were observed between the two subgroups within the experimental group (Supplemental Fig. 1b). Fig. 1 Analysis of survival curves for DOP for conception through non-IVF means (HR = 2.927, 95% CI: 1.390, 6.165; P  = 0.005) Analysis of survival curves for DOP for conception through non-IVF means (HR = 2.927, 95% CI: 1.390, 6.165; P  = 0.005) Univariate Cox regression analysis revealed no significant association between the DOP for conception and other factors, such as female age, BMI, reproductive history, or infertility causes (Supplemental Table 2). Furthermore, in the multivariable Cox proportional hazards model adjusted for female age and BMI, women with ovarian maldescent still exhibited a significantly longer DOP for conception compared to the control group (HR = 3.284, P  = 0.002; Fig.  2 ). Fig. 2 Cox regression analysis of DOP for conception through non-IVF means (including women’s age and BMI correction) Cox regression analysis of DOP for conception through non-IVF means (including women’s age and BMI correction)

In conclusion, our study provides novel insights into the relationship between ovarian maldescent and female fertility. For the first time, we confirmed the detrimental effect of ovarian maldescent on female pregnancy outcomes, thereby establishing a foundation for the development of targeted diagnostic and therapeutic strategies. Given its potential impact on the time required for conception, IVF is recommended for patients with short-term fertility goals, though treatment requires careful management to mitigate OHSS risk.

While the clinical relationship between ovarian maldescent and female fertility has remained poorly understood, this knowledge gap has compromised both comprehensive patient assessment and reliable fertility counselling . This study represents the first systematic investigation into the potential impact of ovarian maldescent on female fertility. Our findings suggest that individualized treatment strategies may be necessary for certain women preparing for conception, emphasizing the importance of tailored care in optimizing their reproductive outcomes . In this study, we revealed that ovarian maldescent significantly impaired female fertility, as indicated by reduced pregnancy rates and prolonged DOP for non-IVF conception. In the control group, women achieved pregnancy approximately three months postsurgery, whereas it took a longer median time of seven months in the ovarian maldescent group. From the perspective of reproductive system anatomy, ovarian maldescent results in abnormal positioning of the ovaries and fallopian tubes, which may prevent the oocyte from being properly captured, meeting sperm, or being transported into the uterine cavity, thus adversely affecting fertility. Additionally, the ovaries may exhibit an elongated morphology, causing the fimbriae of the fallopian tube to capture only eggs expelled from the narrow tip of the ovary, further reducing the likelihood of conception. Notably, one patient in the ovarian maldescent group had a history of ectopic pregnancy, whereas none were reported in the control group. Interestingly, this finding is consistent with prior clinical observations reported by Catarina et al. and Seoud et al., which documented similar associations between ovarian maldescent and ectopic pregnancy [ 18 , 19 ]. Therefore, ovarian maldescent may contribute to an increased rate of ectopic pregnancy, potentially due to factors such as excessive tubal length or impaired rhythmic tubal contractions, which could delay the transport of embryos. However, owing to the limited number of cases, the relationship between ovarian maldescent and ectopic pregnancy warrants further investigation. Furthermore, two cases of pregnancy loss were observed in the experimental group, whereas one case was observed in the control group. Given that pregnancy loss is associated primarily with factors such as embryo quality, infection, immune responses, and the intrauterine environment, there is currently no evidence to suggest a direct correlation between ovarian maldescent and pregnancy loss. Moreover, we suspect that ovarian maldescent may influence the ovarian reserve. Our findings unexpectedly revealed that the anti-Müllerian hormone (AMH) level in the ovarian maldescent group was higher than that in the control group. This could be attributed to the elongation of ovarian tissue, which may have increased the volume of the ovarian cortex and the number of antral follicles, thereby enhancing its ovarian reserve. As a well-established marker of ovarian response, elevated AMH levels are associated with an increased risk of ovarian hyperstimulation syndrome (OHSS) [ 20 , 21 ]. Therefore, in the context of assisted reproduction, a mild ovarian stimulation protocol is recommended for patients with ovarian maldescent to minimize the risk of OHSS. Furthermore, given the challenges in detecting maldescent ovaries via transvaginal ultrasonography, careful monitoring of OHSS is warranted during ovulation induction, particularly when there is a discrepancy between serum estradiol levels and observed ovarian follicular development [ 22 ]. The advancement of in vitro fertilization (IVF) technology has provided renewed hope for women experiencing infertility. Cases of women with ovarian maldescent who conceive via IVF have been reported [ 23 , 24 ]. Van Voorhis et al. confirmed the diagnosis of ovarian maldescent in an infertile woman through HSG and laparoscopy, following which she successfully achieved pregnancy after IVF intervention [ 24 ]. In our follow-up study, no significant difference was observed in pregnancy rates between the two groups of women who conceived through IVF, suggesting a potential impact of ovarian maldescent on oocyte capture and transport. Consequently, for women with ovarian maldescent who desire immediate conception, IVF is recommended as an effective treatment. Additionally, transabdominal oocyte retrieval may increase the success rate of IVF in these patients [ 25 , 26 ]. At present, we propose the idea of releasing the pelvic infundibular ligament near the ovary and fallopian tube to improve its anatomical position. However, clinical implementation of this technique faces two major challenges. First of all, the blood supply of the pelvic infundibular ligament is rich, and this delicate operation is risky and limited for gynecologists without professional training in plastic surgery. Second, due to the very small number of cases, the improvement of subsequent ovarian function and pregnancy outcomes needs to be further confirmed. This study, however, is subject to several limitations. Above all as a single-center study, our findings may have limited generalizability despite using standardized protocols. In addition, while our sample size (21 maldescent cases) is meaningful given the condition’s rarity (0.3–2.3% incidence), it remains relatively small for detecting subtle effects. Future multicenter studies with larger cohorts would help validate our findings. Nevertheless, as one of the largest surgical case series to date, this study provides unique insights into a poorly understood condition that may be overlooked in routine infertility evaluations. While epidemiological generalizability is inherently limited for ovarian maldesent, our rigorously characterized cohort establishes essential baseline data for future research and raises awareness of this underdiagnosed contributor to female infertility.

The gonads initially develop within the genital ridge, which differentiates into testes or ovaries depending on chromosomal sex [ 1 , 2 ]. While testes descend into the scrotum, ovaries normally migrate to the true pelvis between the utero-ovarian and pelvic infundibular ligaments. In ovarian maldescent, the ovary remains positioned above the pelvic rim with an elongated axis, accompanied by corresponding fallopian tube elongation and potential ligament anomalies including shortening of the suspensory ligament or elongation of the utero-ovarian ligament [ 3 – 5 ]. The precise mechanism underlying ovarian maldescent remains unclear, though it is known that gonadal descent is guided by the gubernaculum. Current hypotheses suggest the condition may result from incomplete caudal migration or developmental restrictions in specific components of the genital ridge [ 1 , 3 , 6 – 8 ]. Diagnostic challenges contribute to the uncertain incidence ranging from 0.3% to 2%, as the condition is frequently asymptomatic and often undetected by conventional imaging techniques including ultrasound, magnetic resonance imaging (MRI), and hysterosalpingography [ 4 , 9 , 10 ]. Thus, most documented cases are discovered unexpectedly during abdominal procedures performed for unrelated clinical reasons [ 11 – 14 ], limiting research primarily to case reports [ 3 , 6 ]. The role of ovarian maldescent in female fertility remains a subject of debate [ 3 ]. In 1986, Rock et al. reported four cases of ovarian maldescent, including two successful pregnancies following treatment for other infertility factors [ 15 ]. A subsequent larger study of 2,500 infertility procedures identified five maldescent cases, concluding that while other factors were present, ovarian maldescent’s potential contribution to female infertility could not be excluded [ 16 ]. Further supporting a possible association, Gorgen and colleagues documented a case of unexplained infertility in a 19-year-old woman where hysterosalpingography revealed fallopian tubes extending to the third lumbar vertebra, a finding confirmed by laparoscopy [ 17 ]. Building upon these observations, the current study aims to investigate the relationship between laparoscopically-confirmed ovarian maldescent and fertility outcomes.

Supplementary Material 1: Supplemental Figure 1. The comparison of DOP for conception through non-IVF means in both groups and subgroups. 1a. The ovarian maldescent group and the control group. 1b. The unilateral and bilateral ovarian maldescent subgroup. **: P = 0.001. Supplementary Material 1: Supplemental Figure 1. The comparison of DOP for conception through non-IVF means in both groups and subgroups. 1a. The ovarian maldescent group and the control group. 1b. The unilateral and bilateral ovarian maldescent subgroup. **: P = 0.001. Supplementary Material 2. Supplemental Table 1. Pregnancy outcomes in the unilateral and bilateral ovarian maldescent subgroup. Supplemental Table 2. Univariate COX analysis of the influence of other factors on the DOP for conception through non-IVF means Supplementary Material 2. Supplemental Table 1. Pregnancy outcomes in the unilateral and bilateral ovarian maldescent subgroup. Supplemental Table 2. Univariate COX analysis of the influence of other factors on the DOP for conception through non-IVF means