Unilateral ovarian endometriotic cysts do not impair follicles development, oocyte and embryo quality: report on eight controlled ovarian hyperstimulations and ICSI cycles

Sir, We thank Benaglia et al. (2009) for their interesting study. In contrast to Nakagawa et al. (2008), they found that spontaneous ovulation is impaired in ovaries affected by endometriotic cysts. The same group previously observed hypo-responsiveness of the affected ovaries to gonadotrophin-induced controlled ovarian hyperstimulation (COH) (Somigliana et al., 2006a, b). In all studies, ovulation was only presumed by ultrasound (US) criteria. We report herein on three infertile patients with unilateral ovarian endometriotic cysts diagnosed according to current US criteria (Mais et al., 1993) and undergoing three minimally stimulated (one patient) and five COH ICSI cycles (two patients). All health information regarding the patients have been rendered anonymous and they consented to this publication. Institutional Review Board approval has been obtained for this clinical study. This study is in accordance with the Helsinki Declaration of 1975 regarding human experimentation. Patient #1: L.P. aged 37, secondary infertility, was diagnosed with one 16 mm endometriotic cyst on her right ovary. She was offered a minimally stimulated ICSI cycle using rFSH (Gonal F, Merck Serono, Rome, Italy) and GnRH antagonist (Cetrorelix, Cetrotide, Merck Serono, Rome, Italy) due to severely impaired ovarian reserve (3rd day FSH . 16 mUI/ml, estradiol . 80 pg/ml and antimullerian hormone , 2 pmol/l on two different occasions) and lack of response to COH. In three consecutive ICSI cycles, one follicle reached 17 mm mean diameter and after hormonal and US check, ovulation was triggered by using 10 000 U hCG from two different batches. Cycle #1: one follicle grew from the right ovary, one metaphase II (MII) oocyte was retrieved and microinjected and one firstgrade (top quality) embryo (according to a three-grade score, based on the size and equality of the blastomeres) was transferred. No pregnancy ensued. Cycle #2: the same protocol as for Cycle #1 was used and one follicle grew from the right ovary, but no oocyte was retrieved. Cycle #3: the same protocol as for Cycle #1 was used, one follicle grew from the right ovary, one MII oocyte was retrieved and microinjected and one second-grade embryo was transferred. No pregnancy ensued. Patient #2: A.D., aged 33, primary infertility, was diagnosed with two endometriotic cysts (mean diameter 22 and 12 mm) on her right ovary. After discussing the arguments for and against the surgical removal of endometriomas (Somigliana et al., 2006a, b) and the success rates of intrauterine insemination and ICSI, the patients chose to be treated by ICSI. In two consecutive ICSI cycle, a ‘long’ protocol was offered by using rFSH (Puregon, Organon, the Netherlands) and agonist (buserelin acetate, Suprefact; Aventis Farma, Milan, Italy) and after hormonal and US check, ovulation was triggered by using 10 000 U hCG from two different batches: Cycle #1: 7/10 follicles grew on the right ovary. No oocyte was retrieved; Cycle #2: 6/ 10 follicles grew on the right ovary. Two MII oocytes were retrieved and one second-grade embryo was transferred. No pregnancy ensued. In two other ICSI cycle, a ‘short’ protocol was offered using rFSH and GnRH antagonist (ganirelix, Orgalutran, Organon, the Netherlands) and after hormonal and US check, ovulation was triggered by using 10 000 U hCG from two different batches: Cycle #3: five of eight follicles grew on the right ovary. Five MII oocytes were retrieved and microinjected, and two first-grade embryos were transferred. No pregnancy ensued; Cycle #4: 9/16 follicles grew on the right ovary. Four of five MII oocytes were retrieved from the right ovary. All oocytes were microinjected and two of three oocytes were fertilized from the right ovary. From the right ovary oocytes, one first-grade and one second-grade embryos ensued, while from the left ovary oocyte, one third-grade embryo ensued. All embryos were transferred on Day 2. Pregnancy outcome is still pending. Patient #3: T.D., aged 35, primary infertility, was diagnosed with one 10 mm endometriotic cyst on her right ovary. After seminal fluid and tubal controls, she was offered intrauterine insemination, which was reverted to ICSI due to hyper-responsiveness to low dosage rFSH (Puregon, Organon, the Netherlands). GnRH antagonist (ganirelix, Orgalutran, Organon, the Netherlands) was therefore added to the protocol to inhibit ovulation: four of eight follicles grew on the right ovary. Peak estradiol and LH were found at 1600 pg/ml and 3 mUI/ml, respectively. Ovulation was triggered by using 10 000 U of hCG from two different batches. No oocyte was retrieved. Although no conclusion can be drawn from our small series, we found that 33/55 (60%) follicles grew on the endometriotic cyst affected ovary, whatever the COH protocol used. Interestingly, in our series, oocyte and embryo quality was also checked and found widely optimal (Suzuki et al., 2005). In one cycle (Patient #2, Cycle #4), oocyte and embryo quality from both ovaries were separately assessed and no impaired function, specific to the endometriomabearing ovary, was observed. Instead, the absence of retrieved oocytes in three out of eight (37%) cycles and the absence of pregnancy (one case still pending), despite good embryo quality and young patients’ age in most cases, suggest a general impairment of spontaneous and induced folliculogenesis and/or implantation problems in these patients, independently from the presence of endometriomas, even though Patient #1 (severely impaired ovarian reserve) is excluded from the analysis. These observations may confirm that