EFFECT OF PELVIC ENDOMETRIOSIS, ENDOMETRIOMAS AND RECURRENT ENDOMETRIOMAS ON IVF-ET/ICSI OUTCOMES.

INTRODUCTION: Endometriosis, the most common gynecological disorder, is a challenging disease observed in 20% - 40% of subfertile women.
MATERIAL AND METHODS: 380 women were divided into four groups. Group A consisted of 176 women with pelvic endometriosis. Group B consisted of 125 women who had previously undergone a laparoscopic endometrioma cystectomy. Group C consisted of 38 women with recurrent endometriomas without aspiration before IVF-ET/ICSI. Group D consisted of 41 women with recurrent endometriomas undergone aspiration before IVF-ET/ICSI.
RESULTS: Baseline FSH level (8.61 ± 3.42 mIU/mL) and total dose of Gn (2337.15 ± 853.00 IU) in Group A were the lowest (p < 0.05). The number of retrieved oocytes in Group B (7.98 ± 5.05) was significantly fewer than those in Group A and D (p < 0.05). The numbers of MII oocytes in Groups A, C and D were significantly larger than that in Group B. The number of retrieved oocytes, high-quality embryos, implantation and pregnancy rates were similar in Groups C and D.
CONCLUSIONS: Pelvic endometriosis had a less adverse effect on ovarian reserve than endometrioma. No advantage was found in transvaginal aspiration for recurrent endometriomas before IVF-ET/ICSI.

RCT Entities:   Population Interventions Outcomes

1. INTRODUCTION

Endometriosis, the most common gynecological disorder, is a challenging disease observed in 20% - 40% of subfertile women (1). Endometriomas affect 17 - 44% of women with endometriosis (2, 3, 4). Cystectomy is usually used for endometriomas with diameters larger than 3 cm before assisted reproductive technology (ART) (5). Decreased ovarian reserve might result from surgical procedures (6, 7, 8) or endometriosis itself (9, 10). A reduced response to controlled ovarian hyper stimulation (COH) after cystectomy has been reported in other studies (11, 12).

There is no consensus regarding which treatment is most favorable in terms of preservation of ovarian reserve and subsequent ART outcome (13). Especially for the recurrent endometriomas after surgical resection, there is also no better approach. Transvaginal aspiration may be a choice in these conditions, but a minimal number of reports have been published regarding the management of recurrent endometriomas during in vitro fertilization - embryo transfer/intracytoplasmic sperm injection (IVF-ET/ICSI) cycles. Whether aspiration can improve the outcome of ART before COH remains unknown.

The first aim of this study was to evaluate the ovarian response to COH for IVF-ET/ICSI and the outcome of ART in patients with a history of endometriosis that have been treated once with laparoscopy with or without cystectomy. The secondary aim was to investigate whether aspiration of recurrent ovarian endometriomas before COH improved the prognosis of IVF-ET/ICSI cycles.

2. MATERIALS AND METHODS

2.1 Patients

This retrospective study was obtained ethical pre-approval by the Third Affiliated Hospital of Sun Yat-Sen University Reproductive Medicine Ethic Committee. A total of 380 women with endometriosis who had previously undergone laparoscopic surgery before IVF-ET/ICSI cycles during 2012-2013 were retrospectively identified. Group A consisted of 176 women with pelvic endometriosis but without ovarian endometriomas diagnosed by laparoscopy. Group B consisted of 125 women who had previously undergone laparoscopic endometrioma cystectomy; the endometriomas were not recurrent before IVF-ET/ICSI cycles. Group C consisted of 38 women with recurrent endometriomas after a previous cystectomy; the endometriomas were not aspirated transvaginally before IVF-ET/ICSI cycles. Group D consisted of 41 women with recurrent endometriomas after a previous cystectomy; they underwent aspiration before IVF-ET/ICSI cycles.

2.2 COH protocols

Patients underwent COH with a GnRH-a prolonged protocol or a GnRH-a long protocol. Briefly, the patients who underwent prolonged down-regulation received 1.87 mg or 3.75 mg of Triptorelin (Diphereline, IPSEN, Pharma, France) every 28 days for 1-3 months before COH. As for patients taking long protocols, an injection of 1.0-1.3 mg of GnRH-a (Triptorelin) was administered from the mid-luteal phase of the preceding cycle. Complete pituitary suppression was confirmed by serum E2 level <50 pg/mL and serum LH level <5 mIU/mL.

Recombinant FSH (Gonal-F, Serono, Switzerland) and/or hMG (LiZHu, China) were used at doses ranging between 225 and 450 IU/day. The dosage of FSH and hMG was adjusted according to the ovarian response. Recombinant hCG (Serono, Switzerland) was given to trigger follicle maturation when at least two follicles reached a mean diameter of 18 mm. Oocytes retrieval was performed 34-36 hours after hCG injection. Embryo transfers were performed 3 -5 days later. Pregnancy was diagnosed by a rising concentration of serum β-hCG, which was tested 14 days after ET. Clinical pregnancy was defined as presence of a gestational sac.

2.3 Statistical Analysis

The SPSS statistical software package (version 11.0) was used for statistical analysis. Values are expressed as the mean ± SD. One-way analysis of variance (ANOVA) with a post hoc test using Fisher’s Protected Least Significant Difference (PLSD) was used to compare multiple means from different groups. A χ2-test was used to compare categorical variables. P values <.05 were considered to be statistically significant.

3. RESULTS

3.1 Patient Characteristics and Stimulation Outcomes

A total of 380 women with endometriosis were retrospectively studied. The patient demographic variables were compared in Table 1. The four groups were similar regarding duration of infertility, age, body mass index and endometrial thickness on hCG day. There were significant differences among the four groups for baseline FSH, total dose of Gn, duration of ovulation induction and plasma E2 level on hCG day.

Table 1

Epidemiologic and stimulation characteristics. Note: NS =not statistically significant.

When multiple comparisons were performed by a post hoc test, we obtained the following results: a) the baseline FSH level in Group D was 11.00 ± 6.08 mIU/mL, which was significantly higher than in other groups (P < 0.05); b) the total dose of Gn was significantly lower in Group A (2337.15 ± 853.00 IU) compared to the other three groups (P < 0.05) and c) the duration of ovulation induction for Group A (10.94 ± 2.44 days) was slightly shorter than that of Group C (11.74 ± 2.04 days) and was significantly shorter than those of Group B (11.83 ± 2.55 days) and Group D (12.27 ± 2.46 days). d) in Group A, the E2 level on hCG day was 2975.97 ± 1437.56 pg/mL, which was significantly higher than those of other groups (P < 0.05).

The average diameters of recurrent endometriomas in Groups C and D were both less than 3 cm (12.98 ± 0.60 cm and 19.62 ± 0.93 cm).

3.2 IVF/ICSI Outcomes

As shown in Table 2, the numbers of high-quality embryos and transferred embryos were similar in the four groups. There were significant differences in the numbers of oocytes retrieved and MII oocytes among the four groups. From multiple comparisons with the post hoc test, we found that the number of retrieved oocytes in Group B was 7.98 ± 5.05, which was significantly smaller than those in Groups A and D (P < 0.05). The numbers of MII oocytes in Groups A, C and D were 8.28 ± 4.75, 8.55 ± 4.95 and 8.61 ± 5.61, respectively, which were significantly more than that in Group B. There were no significant differences in implantation rate or pregnancy rate among the four groups.

Table 2

IVF/ICSI Outcomes. Note: NS =not statistically significant.

4. DISCUSSION

The increased prevalence of endometriosis among infertile women indicates that endometriosis impairs women’s reproduction (14). Several mechanisms have been proposed, including distorted pelvic anatomy (15), impaired ovary function (16), altered micro environment (17, 18), affected endo­metrial receptivity (19-21) and reduced oocyte/embryo quality (22, 23). In our study, the baseline FSH level in Group D was 11.00±6.08 mIU/mL, which was significantly higher than those in other groups (P < 0.05). This finding showed that endometriomas, especially the recurrent endometriomas after surgical treatment, have a negative effect on the ovarian reserve.

According to the ESHRE guidelines, ovarian endometrioma (≥3 cm in diameter) removal and histologic diagnosis are recommended to identify endometriosis and to exclude rare instances of malignancy (24). But, the surgical intervention may have a negative effect on the ovarian reserve. Our study showed that after surgical treatment, the baseline FSH level in Group A was the lowest (8.61 ± 3.42 mIU/mL), which indicated that pelvic endometriosis had a less adverse effect on the ovarian reserve than endometrioma. Both the endometriotic ovarian cyst itself and surgical procedures could do harm to the ovaries. Maneschi et al. found a reduced number of follicles antecedent to surgery, suggesting that cysts may damage the ovary by pressing the ovarian cortex. Potential deleterious mechanisms in surgical procedures are the removal of a consistent amount of ovarian tissue during a cystectomy and the adverse changes in ovarian artery blood flow.

There is still controversy regarding the impact of endometriosis on IVF outcome (25, 26). A recent meta-analysis demonstrates that patients with endometriosis-associated infertility undergoing IVF-ET have a 36% reduction of pregnancy rate compared to women with other indications for IVF-ET (27). In our study, the data showed that there were no significant differences in the numbers of high-quality embryos, implantation rate or pregnancy rate among the four groups.

Koga K et al. showed that the recurrence rates of endometrioma after surgical excision were quite variable, ranging from 6 to 30% (28). There is still controversy on how to effectively treat recurrent endometriomas. A matched case-control study from Juan A. Garcia-Velasco et al. showed that a laparoscopic cystectomy for endometriomas before commencing an IVF cycle does not improve fertility outcomes. In our study, 41 women were treated by transvaginal aspiration before IVF-ET/ICSI cycles (Group D), while the others were not treated (Group C). We found that the number of retrieved oocytes, the numbers of high-quality embryos, the implantation and pregnancy rate were similar in the two groups. Our results showed that transvaginal aspiration for recurrent endometriomas (< 3 cm in diameter) before IVF-ET/ICSI cycles does not improve the outcome.

5. CONCLUSION

Our study demonstrated that pelvic endometriosis had a smaller adverse effect on the ovarian reserve than endometrioma. No advantage was found in transvaginal aspiration for recurrent endometriomas (< 3 cm in diameter) before IVF-ET/ICSI cycles in terms of number of retrieved oocytes and implantation and pregnancy rates.