Investigation of the effect of ovarian cysts on clinical pregnancy results in vitro fertilization cycles

OBJECTIVE: In vitro fertilization method is one of the last step procedures used in the treatment of couples who cannot achieve pregnancy. Lately, there has been an increasing demand for advanced age pregnancy and various environmental reasons, delaying pregnancies to a later age. A simple cyst can be detected when starting the in vitro fertilization cycle, especially in women with reduced ovarian reserve and/or advanced age. In this study, clinical pregnancy outcomes of patients with simple cysts on the day of baseline ultrasonography were compared. MATERIALS AND METHOD: The study was conducted after the ethical approval was obtained from the Non-Invasive Studies Ethics Board of Dokuz Eylul University. Within the scope of the study, the data of 273 patients with and without cysts on the IVF cycle start day were evaluated retrospectively, who applied to the Assisted Reproductive Treatment Center, which is affiliated to the Department of Obstetrics and Gynecology of Dokuz Eylül Medical Faculty Hospital, between 2010 and 2020. The case with 137 cysts will be referred to as the case group. 136 participants without cysts were named as the control group. In our study, patients with and without cysts on the basal ultrasonography day at the beginning of the in vitro fertilization procedure were compared in terms of clinical pregnancy outcomes. The group with cysts was divided into three groups as 10-15 mm, 16-20 mm, and those with cysts of 21 mm or more. At the end of the study, it was tried to find the threshold value for the cyst diameter. In the control group, in vitro fertilization cycle was started at similar times to the cyst group, and patients with similar infertility reasons and similar age groups were selected. Based on the 1999 publication of Segal et al., it was planned to screen at least 127 cases with simple cysts and 127 cases without (±10%) for power 80% at 95% confidence level. In the routine records in our hospital; patient's age, gravity and parity, specific obstetric history, cause of infertility, ectopic pregnancy history, comorbidities, previous operation history, previous drug use, smoking, menstrual pain (dysmenorrhea), pain during sexual intercourse (dyspareunia), chronic pelvic pain, hirsutism and galactorrhea was questioned. Ferriman-Gallwey Scoring system was used for hirsutism scoring. Also mentioned in infertility files; AMH level, in-vitro fertilization cycle stimulation regimen, number of right-left and total ovarian antral follicles detected on the basal ultrasonography day, if the cyst is detected on the basal ultrasonography (2nd-4th day of the menstrual cycle), its size, content and in which ovary it is located, again If cyst is present, serum estradiol, LH and progesterone level on the day of basal ultrasonography, in-vitro fertilization induction time, gonadotropin starting dose, total amount of gonadotropin used, ovulation trigger type, ovulation trigger day, if any, estradiol and progesterone level, if present, midluteal estradiol and progesterone, cycle cancellation rate, number of oocytes retrieved, number of embryos formed, number of metaphase 2 (M2) oocytes, fertilization rate, number and grade of embryos transferred, endometrial thickness on the day of embryo transfer decision, clinical pregnancy outcome, live birth rate and use of luteal support ( progesterone, estradiol, GnRH- analogue) created our database. FINDINGS: The patients included in the study were divided into 2 groups as those with cysts of 10 mm and above on the basal ultrasonography day (2nd-4th day of the menstrual cycle) and those without cysts. 137 patients with cysts were taken as the case group, and 136 patients without cysts were taken as the control group. The mean age of the cyst group was 34.93±5.17, and the mean age of the control group was 36.31±4.75 (p=0.022). There was no statistically significant difference between cyst and control group in terms of gravity, parity and AMH variables. The mean induction day was 9.72±2.00 day in the cyst group and 10.24±1.87 day in the control group (p=0.027). The mean total gonadotropin dose was 3193.61±1240.53 in the cyst group and 3593.29±1204.68 in the control group (p=0.007). There was no statistically significant difference between the cyst and control groups in terms of the variables of cycle count, total antral follicle count, ovulation trigger day, number of oocytes collected, number of M2 oocytes, number of fertilized oocytes and number of embryos formed. There was no statistically significant difference between the cyst and control groups in terms of ovulation trigger day E2, LH, progesterone and midluteal serum E2, progesterone, number of embryos transferred, endometrial thickness, baby birth week and baby birth weight variables. While the rate of luteal estrogen usage in the cyst group was 76.64%, it was 81.62% in the control group. Luteal progesterone use is available in both groups. The use of luteal GnRH analog was 43.80% in the cyst group and 32.35% in the control group. The distribution of multiple pregnancy shows a statistically significant difference between the cyst and control groups (p=0.032), with twin pregnancy being 6.57% in the cyst group and 1.47% in the control group. All findings so far have been compared between groups with and without cysts. If we compare the whole group according to clinical pregnancy; the mean age was 36.15±4.99 years in the group without clinical pregnancy and 33.86±4.65 years in the group with no clinical pregnancy (p=0.001). The mean number of total antral follicles was 7.01±4.18 in the group without clinical pregnancy and 9.81±5.77 in the group with no clinical pregnancy (p=0.001). The mean total gonadotropin dose was 3481.82±1282.05 IU in the group without clinical pregnancy and 3101.75±1032.47 IU in the group with no clinical pregnancy (p=0.017). The mean serum LH measured on the ovulation trigger day was 2.95±3.16 mIU/mL in the group without clinical pregnancy and 1.76±1.04 mIU/mL in the group with no clinical pregnancy (p<0.001). The mean of midluteal serum E2 was 499.43±403.07 pg/mL in the group without clinical pregnancy and 767.40±616.15 pg/mL in the group with no clinical pregnancy (p=0.048). The mean of collected oocytes was 6.34±4.25 in the group without clinical pregnancy and 8.52±4.13 in the group with no clinical pregnancy (p<0.001). The mean of metaphase-2 oocytes was 5.08±3.64 in the group without clinical pregnancy and 6.91±3.34 in the group with no clinical pregnancy (p<0.001). The mean of fertilized oocytes was 3.68±3.11 in the group without clinical pregnancy and 4.81±2.54 in the group with no clinical pregnancy (p=0.010). The mean embryo formation was 3.60±2.93 in the group without clinical pregnancy and 4.73±2.53 in the group with no clinical pregnancy (p=0.007). Decreased ovarian reserve, advanced maternal age, male factor, tubal factor, unexplained infertility, anovulation and multiple causes were included as infertility causes. If we examine only the cyst group within itself; estrogen use in the luteal period was 71.43% in the group without clinical pregnancy and 28.57% in the group with no clinical pregnancy. If we examine only the control group in itself; the mean age was 36.93±4.71 in the group without clinical pregnancy and 34.36±4.42 in the group with no clinical pregnancy (p=0.006). The mean number of total antral follicles was 7.14±4.13 in the group without clinical pregnancy and 9.88±5.75 in the group with no clinical pregnancy (p=0.015). The mean serum LH on the day of ovulation trigger was 3.00±2.49 mIU/mL in the group without clinical pregnancy and 1.97±1.10 mIU/mL in the group (p=0.006). The mean serum P4 on the ovulation trigger day was 0.93±0.49 ng/mL in the group without clinical pregnancy and 0.69±0.27 ng/mL in the group with no clinical pregnancy (p=0.004). The mean of midluteal serum E2 was 495.74±270.59 pg/mL in the group without clinical pregnancy and 761.54±496.12 pg/mL in the group with no clinical pregnancy (p=0.018). The mean of midluteal serum P4 was 20.32±14.39 ng/mL in the group without clinical pregnancy and 33.14±16.50 ng/mL in the group with no clinical pregnancy (p=0.011). In the cyst group participants, the mean serum E2 measured on the day the cyst was detected was 65.12±49.21 pg/mL, the mean serum LH measured on the day the cyst was detected was 4.13±2.58 mIU/mL, and the mean serum progesterone on the day the cyst was detected was 0.48 It is ±0.63 ng/mL. If we look at the distribution of E2, LH and P4 values according to cyst diameters; The median cyst LH value was 3.92 mIU/mL (0.89-7.04) in the group with cyst diameter of 10-15 mm, 2.71 mIU/mL (0.68-9.50) in the group with 16-20 mm, and It was 3.80 mIU/mL(0.66-15.20) in the 21 mm and above group (p=0.030). There is no significant relationship with the E2 and P4 variables. When the correlation between cyst diameter and E2, LH and P4 values was evaluated, it was determined that the serum E2 value measured on the day the cyst was detected and the LH value were evaluated (r=0.316), the serum E2 value measured on the day the cyst was detected and the P4 value measured (r=0.257) and the day the cyst was detected. There is a statistically significant correlation between serum LH and P4 value (r=0.335). If we look at the correlation between total antral follicle counts and oocyte counts according to cyst diameters, there is a significant correlation between total antral follicle count and oocyte count in the group with a cyst diameter of 10-15 mm (r=0.626). In the group with cyst diameter of 16-20 mm, there was a lower but still significant correlation between the total antral follicle count and the number of oocytes (r=0.488). In the group with cyst diameter of 21 mm and above, there is no significant correlation between the total number of antral follicles and the number of oocytes. In the comparison of clinical pregnancy status and total antral follicle number according to cyst diameters, in the comparison made in the non-cyst group, the mean of total antral follicles was 9.88±5.75 in patients with clinical pregnancy and 7.14±4.13 in patients without clinical pregnancy (p=0.015). . There was no correlation between groups with cyst diameters of 10-15, 16-20 and 21 and above. The cut-off value determined as a result of the ROC analysis by the cycle cancellation of serum estradiol values measured on the ovulation trigger day was calculated using the Value Youden Index and was determined as 1253 pg/mL. The sensitivity of this cut-off value was 66.7%, the specificity was 62.5%, and the area under the curve (AUC) in ROC analysis was 0.741 (p=0.028). The cut-off value between cyst diameter and cycle cancellation and determined as a result of ROC analysis was calculated using the Value Youden Index and was determined as 14 mm. The sensitivity of this cut-off value was 80.0%, the specificity was 53.8%, and the area under the curve (AUC) in ROC analysis was 0.693 (p=0.006). CONCLUSION: It is still a controversial issue whether cysts detected in ultrasonography at the beginning of the in vitro fertilization cycle affect clinical pregnancy outcomes. According to our findings, the cycle can be started without hesitation for follicle cysts that are 14 mm or less. The serum E2 level measured on the ovulation trigger day, which greatly affects pregnancy outcomes, is also important. Considering the number of antral follicles around the cyst, IVF treatment can be started. Prospective randomized controlled studies with a high number of patients are needed on this subject.