Formation of functional ovarian cysts in IVF cycles does not decrease with prior oral contraceptive use and does not effect ovarian stimulation outcomes

January 2006 to January 2008 analyzed and compared with treatment results from 20 patients with tubal infertility (TI). TABLE 1. Demographic findings of the patients

Hypo- Hypo

Tubal

p

Age (years) 31,35,6 31,54,7 NS Duration of Infertility (years) 6,83,6 6,83,2 NS Weight (kilogram) 61,69,6 65,88,7 NS BMI (kg/m2) 25,33,1 25,83,1 NS FSH (mIU/ml) 0,70,6 6,71,3 0,001 LH (mIU/ml) 1,42,2 6,71,3 0,001 E2 (pg/dl) 30,48,6 33,49,4 NS All underwent ovarian hyperstimulation for IVF/ICSI at the same center. RESULTS: Demographic characteristics of the patients were comparable. Mean duration of stimulation was 13 days in the HH group and 9 days in the TI group, the difference being significant (0.001). Significantly more gonadotropins were used for the stimulation of HH patients (0.03). Peak serum E2 concentration was found to be higher in the TI group.

TABLE 2. Comparision of the outcomes of the groups

Duration of stimulation (day) Total gonadotropins used (IU) Peak E2 (pg/ml) Total Oocyte MII Oocyte Fertilization rate Transfered embryo number Implantation rate Cancellation rate Pregnancy rate Ongoing pregnancy Missed abortion rate Ektopic pregnancy Live birth rate

Hypo-Hypo

Tubal

p

13,02,4 36301685 1044613 6,53,1 5,92,0 81,914,3 2,60,8 38,324,8 323,1 880 225 225 00 450

9,20,8 2501536 2500245 7,73,6 5,42,7 72,919,5 2,80,5 52,525,3 00 1470 214,3 321,4 17,1 857,1

0,001 0.03 0,001 NS NS NS NS NS 0,05 NS NS NS NS NS

We evaluated the proportion of metaphase II (MII) oocytes to total oocytes retrieved in HH patients and found the number which was similar to the TI group. Despite the fertilization and implantation rates were similar in both groups, cansellation rate was higher in HH group (23.8% vs 1). But pregnancy rate and live birth rate were similar. CONCLUSIONS: This present study showed that HH women undergoing IVF/ICSI are good responders.the treatment of HH women with IVF/ICSI did not increase the multiple pregnancy rates over the TI. Supported by: None.

A-342 ASSESSMENT OF EVERY OTHER DAY ADMINISTRATION OF GnRH ANTAGONIST COMPARED WITH DAILY AND ONE DAY ADMINISTRATION IN FRESH IVF CYCLE. S. Kokeguchi, S. Goto, M. Eguchi, Y. Izumi, H. Hashimoto, M. Shiotani. Hanabusa Women’s Clinic, Kobe/Hyogo, Japan. OBJECTIVE: This study was designed to evaluate whether GnRH antagonist (cetrorelix) given every other day could prevent premature luteinization and obtain good pregnancy outcome in women undergoing IVF fresh treatment. DESIGN: Retrospective study. MATERIALS AND METHODS: A total of 96 women receiving ovulation stimulation IVF cycles were allocated three groups according to GnRH antagonist in two multiple pattern doses or single dose (0.25mg each dose) until the day of hCG administration. Thirty-six women with every other day GnRH administration were classified to Group-1. Women

FERTILITY & STERILITYÒ

with daily administration (n¼43) were grouped Group-2, and Group-3 was defined as 17 women with single administration of controlled ovarian stimulation last day. A total of GnRH antagonist was administrated to each woman over 2 times in the Group-1 and over 4 times in the Group-2. Embryo transfer was performed in fresh IVF cycle and other surplus embryos were continued to cultured until day 5 and assess the blastocyst formation rate. RESULTS: Basal FSH, age, periods of controlled ovarian stimulation, amount of FSH/hMG and peak E2 values showed similar trends in the three groups. During FSH/hMG stimulation, 8(22.2%) of 36 women in Group-1 had LH fluctuation, and 2 (25%) out of 8 women with LH fluctuation had premature LH rises(>¼ 10 IU/l) during GnRH antagonist administration. No LH rises were observed in Group-2. There was a LH rise in 1(16.7%) out of 6 women with LH fluctuation in Group-3. Mean number of oocytes retrieval, fertilized, cleavage and good quality embryos were similar in the three groups. No ovulation was occured at oocyte pick-up in the three groups. Blastocysts were obtained 43(51.8%) out of 83 embryos in the Group-1 as same number as 64(50.8%) out of 126 embryos in the Group-2. Clinical pregnancy rate with fresh embryo transfer was 36.1% (13/36) in the Group-1 and 29.4%(5/17) in the Group-3. The PR in the Group-1 was relatively higher than the PR(14.0%, 6/43) in Group-2 (p<0.05). CONCLUSIONS: Every other day GnRH antagonist administration is as effective as daily administration in terms of oocytes retrieval and early cleavage rate and blastocyst formation rate. This study shows that alternate day administration of GnRH antagonist protcol may increase the some risk of premature LH rise, but may increased pregnancy outcome of fresh cycle embryo transfer compared with daily administration protocol. Supported by: None.

A-344 FORMATION OF FUNCTIONAL OVARIAN CYSTS IN IVF CYCLES DOES NOT DECREASE WITH PRIOR ORAL CONTRACEPTIVE USE AND DOES NOT EFFECT OVARIAN STIMULATION OUTCOMES. Z. Khan, R. P. Gada, S. B. Hudson, N. L. Rollene, E. A. Stewart, C. C. Coddington. OB/GYN, Reproductive Endocrinology and Infertility, Mayo Clinic, Rochester, MN. OBJECTIVE: To determine if functional ovarian cysts are decreased by oral contraceptive use prior to GnRH agonist long luteal protocol. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: All patients undergoing ART in 2004 and 2006 who gave IRB consent were considered for analysis. Patients who took oral contraceptive pills (OCP) for at least 30 days prior to their IVF cycle were compared to those who did not take any OCP’s. The incidence of functional cyst formation after GnRH agonist long luteal protocol was calculated for both groups. Cysts were defined as functional if the baseline estradiol level was >35 pg/mL. In each case of a functional cyst, one of the following decisions was made (a) continuing GnRH agonist therapy for 7-14 days prior to stimulation, (b) aspirating the cyst, (c) continuing with the stimulation or (d) cancelling the cycle. After ovarian stimulation the peak E2 level and the number of total and mature oocytes retrieved were recorded. Data were analyzed using chi square, ANOVA and student t-test. RESULTS: Of 192 IVF cycles, 32 patients were found to have ovarian cysts prior to starting GnRH agonist and were excluded. The incidence of functional ovarian cyst formation was 7.5% (12/160). Prior OCP use did not decrease the incidence of functional cyst formation (Table 1). In 12 IVF cycles a functional cyst was noted. GnRH agonist was continued for 7-14 days in 8/12 cycles. The cycle was continued with stimulation in two cases, cyst aspiration was performed in one case and one cycle was cancelled. No difference was seen in peak E2 levels and number of total and mautre oocytes retrieved in patients with functional cysts vs. those without cysts (Table 2).

TABLE 1. Development Of Functional Cysts

No prior OCP use Prior OCP use

Patients Without Cysts

Patients With Cysts

91 57

7 5

p value¼0.83.

S481

TABLE 2. Ovarian Stimulation Outcomes

Patients Without Cysts

Patients With Cysts

p-value

2101 14.9 10.74

2487 14.0 9.73

0.28 0.82 0.58

Peak E2 level Total Oocytes Mature Oocytes

RESULTS: There were no significant differences between two groups in the cycle cancellation rate,duration of stimulation, consumption of gonadotropin ampules and number of retrieval oocytes,metaphase II oocytes and transferred embryos.Chemical and clinical pregnancy rates were the same in two groups.Ongoing pregnancy rate appeared higher and abortion rate was lower in antagonist group.Although, differences were not statistically significant. TABLE 1. Stimulation and cycle outcomes

CONCLUSIONS: The incidence of functional cyst formation in our study was consistent with numbers reported in the literature. In our patient population, functional cysts developed even with prior OCP use which has not been previously reported. Functional cysts can lead to impaired ovarian stimulation and contribute to poor IVF outcomes. In our study, ovarian stimulation was not affected if a clinical intervention was performed. Supported by: None. A-346

Antagonist (n¼35)

A-347 COMPARISON OF GnRH (GONADOTROPIN-RELEASING HORMONE) ANTAGONIST VERSUS LONG GnRH AGONIST PROTOCOL IN POOR RESPONDERS UNDERGOING IVF (IN VITRO FERTILIZATION). A. Fazel, A. Samiei, E. S. Tehrani Nejad, B. H. Rashidi. Royan Institute, Tehran, Islamic Republic of Iran; Royan Institute, Tehran University of Medical Sci., Tehran, Islamic Republic of Iran; Tehran University of Medical Science, Tehran, Islamic Republic of Iran. OBJECTIVE: To compare the efficacy of GnRH antagonist protocol versus GnRH agonist protocol in poor responders undergoing IVF. DESIGN: Prospective study. MATERIALS AND METHODS: 70 poor responders were randomized into two groups:one group received 0.25mg of Cetrorelix Acetate(Cetrotide),sc(sub cutaneous)daily starting when the largest follicle had reached a diameter of 14mm; the other group received a daily dose of 0.5mg Buserlin Acetate(Superfact),sc starting at the mid-luteal phase of the preceding cycle.On the third day of the cycle,in both groups,ovarian stimulation was commenced with a fixed daily dose of hMG(Human Menopausal Gonadotropin) (300 IU daily).

S482

Abstracts

P-value

Duration of Stimulation (days) 10.111.85 10.062.90 0.922 Total Gonadotrophin 42.5717.62 40.0614.20 0.513 Consumption(ampules) Retrieval oocytes 4.062.31 5.313.80 0.100 Metaphase II oocytes 3.262.31 4.173.12 0.169 Embryos 2.691.55 3.032.19 0.472 Values are expressed as meanSD or number(percentage),and analysed by t-test , x2 or Fisher’s exact test where appropriate.

LUTEINIZED UNRUPTURED FOLLICLE SYNDROME: CLINICAL SYNDROME OF LACK OF HCG ADMINISTRATION AT OOCYTE RETRIEVAL? C. Godby, A. Bertche, P. Warikoo, K. Reynolds, G. Hofmann. Obstetrics and Gynecology, Bethesda Hospital, Cincinnati, OH; Bethesda Hospital, Cincinnati, OH. OBJECTIVE: To determine standard serum hCG levels immediately prior to ovum retrieval after IM or SQ delivery in women undergoing ovum retrieval, after a proven egg donor had no oocytes retrieved and a non-detectable serum hCG level at the time of oocyte retrieval. DESIGN: Prospective collection of serum at the time of oocyte retrieval from women receiving either IM or SQ hCG injections to trigger ovulation prior to ovum retrieval. MATERIALS AND METHODS: Serum was collected 36 hours after hCG administration in 66 IVF women receiving 10,000 IU hCG and from 29 ovum donors receiving 6750 IU SQ. Institutional approval was obtained. Using regression analysis, serum hCG levels were compared to body mass index (BMI), peak estradiol (E2), the number of oocytes retrieved, fertilization rates, and the number of high quality embryos available for transfer. RESULTS: Serum hCG levels were higher in the IM group (mean  standard deviation: 183  91 mIU/mL) compared to SQ (104  55 mIU/mL, P¼0.0001). BMIs were also higher in the IVF group (IVF: 26.6  6.4 vs 22.8 , P¼0.0001). In the IM group only, the BMI was correlated with serum hCG levels (P¼0.001). Serum hCG levels were not correlated with the serum peak E2, number of oocytes retrieved, fertilization rates, or number of high quality embryos available for transfer (P > 0.05). CONCLUSIONS: The failure to retrieve oocytes from these donors was not due to Luteinized Unruptured Follicle Syndrome (LUF), but lack of administration of hCG as instructed. The serum levels described here will allow practitioners to have baseline levels in the event that no, or many fewer than expected, oocytes are retrieved. Supported by: None.

Agonist (n¼35)

TABLE 2. Pregnancy outcomes

Antagonist

Agonist

P-value

Chemical pregnancy(bHCG) 28.1% 28.1% 1.000 clinical pregnancy(gestational sac) 28.1% 28.1% 1.000 Ongoing pregnancy(>12weeks) 100% 77.8% 0.471 Abortion 11.1% 33.3% 0.576 Values are expressed as meanSD or number(percentage),and analysed by t-test , x2 or Fisher’s exact test where appropriate. CONCLUSIONS: A flexible multi-dose GnRH antagonist protocol is feasible for patients who are poor responders on a long agonist protocol;however, our study failed to demonstrate an overall improvement in ovarian responsiveness.Clinical outcomes may be improved by developing more flexible antagonist regimens,an approach that requires further evaluation. Supported by: None.

POLYCYSTIC OVARY SYNDROME A-348 METFORMIN ASSOCIATED TO CLOMIPHENE CITRATE FOR CLOMIPHENE CITRATE-RESISTANT WOMEN WITH PCOS IMPROVES OVULATORY AND PREGNANCY RATES. A RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED STUDY. R. C. Machado, S. Geber. Obstetrics and Gyanaecology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. OBJECTIVE: To evaluate the effect of metformin associated to clomiphene citrate (CC) on ovulation, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, double-blind, placebo-controlled study. MATERIALS AND METHODS: A total of 67 patients with PCOS who received 2 cycles of CC (100 mg/day from days 5 to 9) were initially included in the study. Patients who did not respond to CC were randomly allocated to receive either metformin 850 mg twice daily (group 1) or placebo twice daily (group 2) for two months. After that, CC (100 mg/day from days 5 to 9) was associated for the two following cycles, in both groups. Insulin, glucose, glucose/insulin ratio, testosterone, DHEAS, FSH, LH, body mass index (BMI), endometrial thickness, ovulation, and pregnancy rates were evaluated. RESULTS: A total of 36 patients were resistant to CC. In the metformin group, 15/21 (71.4%) women ovulated, and 8/21 (38.1%) conceived. In the control group, 5/15 (33.3%) women ovulated and 3/15 (20%) conceived. Compared with the control group, the metformin group had significantly higher ovulation (P ¼ 0.04), however, there was no significant difference in the pregnancy rate between the two groups. When patients

Vol. 90, Suppl 1, September 2008