Pregnancy results after fresh embryo transfer and selective frozen-thawed embryo transfer: Single-center experience

Journal Pre-proof PREGNANCY RESULTS AFTER FRESH EMBRYO TRANSFER AND SELECTIVE FROZEN-THAWED EMBRYO TRANSFER: SINGLE-CENTER EXPERIENCE Aytek Sik, Serkan Oral, Yilda Arzu Aba, Ozan Ozolcay, Mehmet Koc, Alper Sismanoglu

PII:

S2468-7847(20)30034-9

DOI:

https://doi.org/10.1016/j.jogoh.2020.101707

Reference:

JOGOH 101707

To appear in:

Journal of Gynecology Obstetrics and Human Reproduction

Received Date:

8 May 2019

Revised Date:

23 January 2020

Accepted Date:

27 January 2020

Please cite this article as: Sik A, Oral S, Aba YA, Ozolcay O, Koc M, Sismanoglu A, PREGNANCY RESULTS AFTER FRESH EMBRYO TRANSFER AND SELECTIVE FROZEN-THAWED EMBRYO TRANSFER: SINGLE-CENTER EXPERIENCE, Journal of Gynecology Obstetrics and Human Reproduction (2020), doi: https://doi.org/10.1016/j.jogoh.2020.101707

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PREGNANCY RESULTS AFTER FRESH EMBRYO TRANSFER AND SELECTIVE FROZEN-THAWED EMBRYO TRANSFER: SINGLE-CENTER EXPERIENCE

CLINICAL RESULTS AFTER FRESH EMBRYO TRANSFER AND FROZENTHAWED EMBRYO TRANSFER: SINGLE-CENTER EXPERIENCE Aytek Sika, Serkan Orala, Yilda Arzu Abab, Ozan Ozolcayc, Mehmet Koca, Alper Sismanoglua a

Department of Reproductive Endocrinology and Infertility, Sisli Kolan International Hospital, Istanbul,Turkey b

Bandirma Onyedi Eylül University, Faculty of Health Sciences, Balıkesir, Turkey

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Department of Reproductive Endocrinology and Infertility, Istanbul IVF Center, Istanbul, Turkey

Aytek Sik : [email protected]

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Serkan Oral: [email protected]

Ozan Ozolcay: [email protected] Mehmet Koc: [email protected]

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Alper Sismanoglu: [email protected]

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Yilda Arzu Aba: [email protected]

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Corresponding Author: Assoc. Prof. Yilda Arzu ABA

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Adress: Bandirma Onyedi Eylül University, Faculty of Health Sciences, Balıkesir, Turkey. Phone: +90266 717 0117 (4504) Gsm: +905055670483 Fax: +90266 7186414 E-posta: [email protected]

ABSTRACT

Objective: To compare the clinical pregnancy and live birth results of fresh embryo transfer (ET) and selective frozen embryo transfer (sFET) in cohort of infertile patients aged between 18-42 years of age in single IVF center.

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Materials and methods: In this retrospective cross-sectional study, the clinical and live birth results of 620 fresh embryo transfer cycles and 580 frozen embryo transfer cycles were investigated in Sisli Kolan International Hospital Fertility Unit between 2015-2018. Results: Age, BMI, causes of infertility, duration of infertility, ovulation induction protocols, the number of oocytes collected and the thickness of endometrium on the day of transfer were similar in the ET and sFET groups. More good quality embryos were obtained in sFET group. The clinical pregnancy and live birth rates were 71.04% and 59.31% in the sFET groups, and

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56.77% and 44.52% in the ET group, respectively (p<0.05). Conclusion: Pregnancy, clinical pregnancy and live birth rates were higher in frozen embryo transfer cycles than in fresh embryo cycles. However, appropriate in vitro fertilization and

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embryo transfer methods suitable for each patient should be determined before choosing fresh ET or sFET treatment modalities.

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Keywords: Fertilized oocyte, mature oocyte, fresh embryo transfer, frozen-thawed embryo

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transfer, pregnancy, infertility

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Introduction

In recent years, there has been an increase in selective frozen embryo transfer (sFET) frequency in in vitro fertilization (IVF) treatments [1]. According to research by the Society for Assisted Reproductive Technology (SART), the number of sFET cycles increased by 82.5% between 2006 and 2012. This rate is higher than that of fresh embryo transfer (ET) cycles. In recent research, sFET cycles accounted for 32.4% of all IVF and intracytoplasmic sperm injection

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(ICSI) cycles [2]. There are 4 main reasons for the increase in sFET cycles; (a) improvement in the technology of embryo freezing and thawing and increase in successful results, (b) a rapid increase in single-embryo transfer with preimplantation genetic diagnosis (PGD) and increase in the number of embryos that are available for freezing, (c) asynchronization between endometrium and transferred embryos as a result of morphologic and biochemical changes in endometrium caused by increased estradiol (E2) and progesterone (P4) levels in the follicular phase in controlled ovarian stimulation (COH), (d) the observation of positive perinatal and

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neonatal results in sFET cycles in many studies [3,4,5,6]. Live birth rates were reported as significantly higher in sFET groups in some publications [7,8], whereas others found no statistically significant difference between ET and sFET groups [9,10].

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Except for live birth rates, there is no clear proven superiority between ET and sFET cycles in terms of other clinical results such as implantation, biochemical pregnancy, clinical pregnancy,

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abortion rates, and the incidence of moderate-severe ovarian hyperstimulation syndrome

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(OHSS) [7-12]. The aim of this study was to compare the clinical results of ET and sFET cycles in infertile patients aged between 18-42 years of age who had applied for IVF treatment in a

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single IVF Center.

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Materials and methods Study design and participants The research was conducted by one physician in Sisli Kolan International Hospital Fertility Unit between June 2015 and May 2018. Patient files were retrospectively examined. 1200 infertile patients with various infertility etiology for IVF who were treated with fresh ET and sFET cycles were included in the study. It was determined that ET cycles were performed in

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620 patients and sFET cycles were performed in 580 patients. Patients with or without uterine abnormalities requiring a surrogate mother, with endometrium thickness below 7 mm during embryo transfer, with Asherman syndrome, with controlled ovarian hyperstimulation (COH) cycles and received an agonist protocol, patients who needed oocyte donors, patients with

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endocrine disorders (hypothyroidism, hyperthyroidism, diabetes mellitus, hyperprolactinemia),

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with previous chemotherapy and radiotherapy, patients aged under 18 or over 42 years, patients with azoospermia and no sperm detection in testicular sperm extraction (TESE)/microscopic

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TESE, patients with embryos performed preimplantation genetic diagnosis (PGD)/next generation genetic sequencing (NGS), and patients without good quality (grade A) 5th day

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blastocyst embryo were excluded from the study. All patients were fertilized by intracytoplasmic sperm injection (ICSI) regardless of the infertility reason. We included the

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pregnancy results of every patients once and there is no patient with fresh ET and concomitant sFET. This means that we do not calculated the cumulative pregnancy rates but just the

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pregnancy rates after single transfer for each patient. The following protocols were used in ovarian stimulation in ET and sFET cycles, oocyte retrieval, and evaluation of clinical results in all participants (Figure1). Ovarian stimulation and oocyte retrieval protocol All patients were called for follow-up on the 2nd or 3rd day of the menstrual cycle. Uterus, ovaries, and endometrium were evaluated using transvaginal ultrasonography (TVUSG), and

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COH with gonadotropins was performed. When the size of ovarian follicles in ultrasonography reached 13-14 mm and/or endometrium thickness was 7 mm, Gonadotropin releasing hormone (GnRH) antagonist, Cetorelix (Cetrotide, Merck, Germany) was added to treatment with a dose of 250 µg/day. When three or more follicles were detected in the ovaries with 17-18 mm diameter during ultrasonographic follow-up every 24 hours, intramuscular/subcutaneous (IM/SC) 5000 hCG (Choriomon 5000 IU, IBSA, Switzerland) was performed and ultrasonography-guided oocyte

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retrieval was performed after 34-36 hours. Blood estrogen and progesterone (P4) levels in all participants were measured using a VIDAS automated immunoanalyzer (bioMerieux, France) prior to hCG injection.

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In patients with serum estrogen levels more than 2500 ng/mL, GnRH agonist (triptoreline

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acetate, Gonapeptyl 0.1 mg/mL, Ferring, Germany) was administered 1 x 0.2 mg/mL SC instead of hCG 34-36 hours prior to oocyte retrieval. These group of patients were directly included in

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the sFET group in order to decrease ovarian hyperstimulation syndrome. In patients with no risk for hyperstimulation syndrome (estrogen levels less than 2500 ng/mL on hCG trigger day)

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the triggering of ovulation was performed with SC 5000 hCG (Choriomon 5000 IU, IBSA, Switzerland) 10000 IU in total. In this group of patients the serum progesterone level was

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determining factor for sFET or fresh ET. Patients with serum P4 levels above 1.2 ng/mL

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underwent sFET and below ≤1.2 ng/mL underwent ET. Embryo transfer process and reproductive success When oocyte retrieval was completed, oocytes were collected for fertilization in a medium (Life Global) and placed in a Miri Benchtop incubator (ESCO) until the intracytoplasmic sperm injection (ICSI) was performed approximately 3-4 hours after the procedure. After the ICSI process, all oocytes were placed in a medium in which 10% life global protein supplement was

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added and the medium of the developing embryos was refreshed; they were monitored until the 5th day. Good quality (Grade A) 5th day blastocyst embryos were transferred in both groups. Embryo classifications was described according to embryo evaluation criteria proposed by ESHRE/ALPHA consensus. The grade A embryos described as expanded blastocyst is greater volume than original volume of the embryo and Zona pellusida (ZP) is very. The grade A embryos also was with a tightly

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packed Inner Cell Mass (ICM) with many cells and trophoectoderm (TE)cells was with many cells forming a cohesive epithelium or TE cells was herniating through a breach in the thinned ZP.

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According to the local rules two embryos were transferred only to patients who were aged over 35 years, those who had previously tried 2 and more times and failed. One embryo was

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transferred to patients outside of these parameters.

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With guidance of transabdominal ultrasound and with a full bladder, fresh cycle embryos were transferred 5 days after ICSI was performed and frozen embryos were transferred on the 20th

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day of the menstrual cycle after the endometrial preparation with estradiol valerate. As a luteal phase support for patients in ET cycles, Estrofem 2 mg tablet (estradiol valerate, Nova Nordisk, Denmark) oral twice daily, Crinone 8% gel (progesterone 90 mg, Merck, UK) intravaginal once

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daily and Progestan 50 mg ampule (progesterone 50 mg, Koçak Farma, Turkey) IM once daily

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were administered. With guidance of transabdominal ultrasound and with a full bladder, fresh cycle embryos were transferred 5 days after ICSI was performed. If the pregnancy test was positive, administration of estrogens was discontinued and administration of P4 as intravaginal and IM was continued until the 12th week of pregnancy in fresh cycles and estradiol valerate plus progesterone administration was continued at the same doses in sFET group patients.

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In sFET cycles, all embryos were frozen through vitrification for cryopreservation. After two menstrual cycles passed from oocyte retrieval, patients were invited for a follow-up on the 2nd day of the menstrual cycle. Ovaries, uterus, and endometrium were checked using TVUSG. Estradiol valerate 2 mg/day was started twice daily and was continued from the 2nd to the 15th day of the menstrual cycle with increasing doses. On the 15th day of the menstrual cycle, when endometrium thickness was 7 mm or above, P4 was started and the dose of estrogen was reduced. After 5 days of P4 administration, with guidance of transabdominal ultrasound and

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with a full bladder, frozen embryos were transferred on the 20th day of the menstrual cycle starting the progesterone administration on the 15th day of the cycle.

A pregnancy test was performed 12 days after the embryo transfer by measuring hCG in the

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blood. A hCG value >5 U/mL was accepted as a positive pregnancy test. Biochemical pregnancy was defined as hCG values of more than 5 U/mL and no viable pregnancy on

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transvaginal ultrasound, 4 weeks after the embryo transfer.

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Clinical pregnancy was defined as the presence of a live fetus and/or a gestational sac in ultrasonography 4 weeks after embryo transfer. Gestational age >22 weeks was accepted as a live birth. After fetal heart beats were heard in ultrasonography, infants born before 22

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gestational weeks were considered as abortions.

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Fig. 1. Consort diagram of the study

1200 infertile patients

620 fresh embryo transfers

580 frozen embryo transfers

244 patients pregnancy (-)

148 patients pregnancy (-)

432 patients pregnancy (+)

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376 patients pregnancy (+) 4 patients ectopic pregnancy (-)

20 patients biochemical pregnancy (+)

20 patients biochemical pregnancy (+)

48 single pregnancy abortion

28 twin pregnancy abortion

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276 patients live birth

40 patients twin pregnancy live birth

68 patients abortion

40 single pregnancy abortion

28 twin pregnancy abortion

344 patients live birth

272 patients single pregnancy live birth

72 patients twin pregnancy live birth

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236 patients single pregnancy live birth

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76 patients abortion

412 patients clinical pregnancy (+)

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352 patients clinical pregnancy (+)

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Statistical analysis

In this study, statistical analysis was performed using the NCSS (Number Cruncher Statistical System) 2007 statistical software (Utah, USA) package program. Descriptive statistical methods (mean, standard deviation, median and interquartile range), independent t-test in the comparison of two groups with normal distribution, the Mann-Whitney U test in the comparison of two groups without normal distribution, and the Chi-square test in the comparison of

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categorical variables were used. Multivariate and univariate analysis of the risk factors affecting the results of sFET were determined using logistic regression analysis. The results were evaluated as statistically significant if p<0.05. Results Of the patients included in the study, 620 (51.7%) underwent ET cycles and 580 (48.3%) received sFET cycles. There was no significant difference between the ET and sFET groups in terms of the mean age of the females and males (p=0.39 and p=0.12, respectively), body mass

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index (BMI) (p=0.46), duration of infertility (p=0.85) (Table 1). The presence of polycystic conditions on the ovaries was more common in the sFET group than in the ET group (p=0.00). There was no statistically significant difference between the etiologic distribution of the ET and

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sFET groups (p=0.93). Demographic and etiologic features of the ET and sFET Groups are shown in Table 1.

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There was no statistically significant difference between the ET and sFET groups in terms of

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the number of antral follicles (AF) on the 3rd day of menstrual cycle (p=0.44), endometrial thickness (p=0.39), level of follicle-stimulating hormone (FSH) (p=0.54), level of luteinizing

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hormone (p=0.89), E2 level (p=0.95), duration of stimulation (p=0.10), and endometrial thickness on the day of transfer (p=0.39). hCG day E2 value, hCG day P4 value, number of oocytes collected, number of mature oocytes, number of fertilized oocytes, and number of

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transferred embryos were significantly higher in the sFET group than in the ET group (p=0.00).

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The clinical features of the patients are shown in Table 2. The rate of pregnancy and clinical pregnancy was statistically higher in the sFET group than in the ET group (p=0.00, p=0.00). There was no statistically significant difference between the ET and sFET groups in terms of biochemical pregnancy, ectopic pregnancy, and abortion rate (p=0.36, p=0.28, and p=0.48, respectively). The presence of live birth, single live birth, and

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twin live birth was statistically higher in the sFET group than in the ET group (p=0.03, p=0.04, and p=0.03, respectively) (Table 3). The presence of polycystic ovaries on the ultrasonography or patients diagnosed with polycystic ovarian syndrome (p=0.00), hCG day E2 value (p=0.00), hCG day P4 value (p=0.00), number of oocytes collected (p=0.00), number of mature oocytes (p=0.00), number of fertilized oocytes (p=0.00), number of transferred embryos (p=0.00), pregnancy result (p=0.00), clinical pregnancy (p=0.00) and presence of live birth (p=0.03) were statistically higher in the sFET

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group than in the ET group. The multivariate logistic regression analysis showed that hCG day E2 value (p=0.00), hCG day P4 value (p=0.00), number of mature oocytes (p=0.04), and number of transferred embryos were the factors affecting the sFET group (p=0.00) (Table 4).

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Discussion

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The increase sFET frequency in in vitro fertilization treatments brings the question of do we really need to freeze all of the embryos during fresh cycle and transfer them in a non-stimulated

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cycle? Many studies have been done to answer this question till this time. In a study by Ata and Seli it was stated that sFET seems to have limited potential to improve effectiveness of

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assisted reproductive technology, which could be limited to hyper-responders. Other suggested advantages of sFET include better obstetric and perinatal outcome. It was also said that in recent

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studies frozen embryo transfers can be associated with serious complications including

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hypertensive disorders during pregnancy, placenta accreta, or increased perinatal mortality [14]. Increasing tendency for sFET also attracts the patients for such a treatment because there are studies that show better pregnancy results if sFET is performed especially in a high responder group patient [15]. Even though assuming that pregnancy results were equivalent in a study by Stormlund et al. nearly 60% of the participants were in favor of sFET compared with fresh embryo transfer [16]. In a recent Cochrane Review the pregnancy rates between ET and sFET were analyzed and it was found that there is just moderate-quality evidence showing that

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one strategy is not superior to the other [6]. In another recent review by Bosdou et al. was stated that in high responders, a significantly higher probability of live birth was observed in the sFET group when compared with the fresh ET group. However, the probability of live birth was not significantly different between the sFET group and the fresh ET group in normal responders [17]. Adopting Freeze-all strategy can contribute to improve delivery outcome after IVF, in terms of clinical live birth rates. In another study was found that higher number of vitrified blastocysts is associated with higher clinical live birth rates in women <40 years old-

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normal/high responders- following Freeze-all policy. The number of the total cryopreserved blastocysts produced might reflect the quality of the oocyte and can successfully predict the pregnancy outcome [18]. In our study we aimed to investigate the difference between sFET and

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fresh ET in a large number of general infertile population without considering the infertility reasons. In a study that was conducted in Belgium by Masschaele T. et all states that there is

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no influence of the indication of freeze-all strategy on subsequent outcome to frozen-thawed

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embryo transfer cycle [19]. Besides these findings the need for universal sFET it is unclear especially in a general infertile population. In our current retrospective study 1200 patients treated for various infertility reasons for IVF we found that sFET gives better pregnancy and

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live birth results in the first IVF cycle. The largest randomized studies comparing fresh ET and sFET in high responding patients like polycystic ovarian syndrome (PCOS) patients are

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showing us that pregnancy results are better with sFET in this subgroup of infertile population

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[6, 20]. In our study we did not divided patients in subgroups in order to see what the pregnancy results in a general infertile population are if sFET or ET is done. We retrospectively analyzed the IVF data of 1200 infertile patients with various IVF indications and saw that the pregnancy results with sFET are better than ET. We had more PCOS patients in the sFET group, because of the risk for ovarian hyperstimulation syndrome with higher number of collected oocytes and good quality embryos for transfer. The increased number of high responders in sFET may be

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the reason for increased pregnancy rates and this is the limitation of our study. Besides this in our study we have included only patients with good quality embryos for transfer and this means that having good quality embryos for transfer gives better pregnancy results in sFET group compared to good quality embryos transferred in a fresh cycle regardless of the infertility etiology. In IVF treatment today, the mechanism of the effect of increased P4 levels on pregnancy outcomes is still controversial [21-23]. Several studies have shown that there are different

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threshold levels between 0.9-3 ng/mL for the negative effects of increased P4 levels in cycles of Assisted Reproductive Technology (ART) [24]. Park et al. examined the factors that contributed to the increase in P4 levels on the day of hCG injection in 2015. These factors

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included estradiol levels on the day of hCG injection, number of follicles ≤14 mm, number of oocytes obtained with a puncture, and ovarian sensitivity [25]. In another study performed in

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1896 patients, there was no association between hCG injection day, clinical pregnancy, and

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high P4 levels. This study was also conducted as a prospective study [26]. In our study, fresh embryo transfer was performed if the P4 level was below 1.2 ng/mL on the hCG day and sFET

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was performed if the P4 level was above 1.2 ng/mL on the hCG day. In patients with high levels of E2 and P4 on the hCG day, sFET was performed and higher pregnancy rates were obtained.

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In patients with high levels of E2 and P4 on the hCG day, sFET was performed and higher pregnancy rates were obtained.

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We did not find any statistically significant difference in terms of miscarriage rates between the fresh ET and sFET group of patients. For this reason, having better pregnancy results with higher number of good quality embryos in sFET group of patients in our study reminds that the impaired endometrial receptivity may be the only reason of lower pregnancy rates in fresh ET group of infertile patients. This shows us that we can achieve favorable pregnancy results in

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different subgroups of infertile patient population only with good quality embryos choosing especially sFET without doing preimplantation genetic screening. Conclusion In our study, the pregnancy, clinic pregnancy and live birth rates in the sFET group was higher than in the ET group in women treated with IVF in our IVF unit. This study also shows that we should not hesitate to cancel fresh ET because of high E2 levels on day of hCG triggering. By

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this way we can decrease ovarian hyperstimulation syndrome in risky patients giving them a favorable and possibly better pregnancy results with freezing all day 5 good quality embryos and transferring them in a non stimulated cycle with serum hormonal status closer to the physiological levels. The more oocyte collected the more fertilization and this means better

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quality embryos for embryo transfer. However, the costs for IVF treatment are high and there

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is also a need for a specific time and energy requirement for infertile couples. For this reason, an individual treatment approach should be applied, the factors affecting infertility should be

Conflict of interest

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determined for each patient, and the most appropriate treatment method should be chosen.

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None of the authors has any financial or personal relationships that could inappropriately

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influence or bias the content of the paper.

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No conflict of interest was declared by the authors.

Financial disclosure: The financial support of this work has been covered by the authors.

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[18] Papanikolaou E, Chartomatsidou T, Timotheou E, Tatsi P, Katsoula E, Vlachou C, et al. In Freeze-All Strategy, Cumulative Live Birth Rate (CLBR) Is Increasing According to the Number of Blastocysts Formed in Women <40 Undergoing Intracytoplasmic Sperm Injection (ICSI). Front Endocrinol (Lausanne). 2019; 3(10):427. [19] Masschaele T, Vandekerckhove F, De Sutter P, Gerris J. No influence of the indication of freeze-all strategy on subsequent outcome to frozen-thawed embryo transfer cycle. Facts Views Vis Obgyn. 2018;10(2):85-91.

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[26] Martinez F, Rodriguez I, Devesa M, Buxaderas R, Gómez MJ, Coroleu B. Should progesterone on the human chorionic gonadotropin day still be measured? Fertil Steril.

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Fig. 1. Consort diagram of the study

1200 infertile patients

620 fresh embryo transfers

580 frozen embryo transfers

244 patients pregnancy (-)

148 patients pregnancy (-)

432 patients pregnancy (+)

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376 patients pregnancy (+) 4 patients ectopic pregnancy (-)

20 patients biochemical pregnancy (+)

20 patients biochemical pregnancy (+)

48 single pregnancy abortion

28 twin pregnancy abortion

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276 patients live birth

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236 patients single pregnancy live birth

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76 patients abortion

412 patients clinical pregnancy (+)

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352 patients clinical pregnancy (+)

40 patients twin pregnancy live birth

68 patients abortion

40 single pregnancy abortion

344 patients live birth

272 patients single pregnancy live birth

72 patients twin pregnancy live birth

28 twin pregnancy abortion

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Table 1. Demographic and Etiologic Features of the ET and sFET Groups ET Group (n=620)

sFET Group (n=580)

Demographic and Etiologic Features

Mean±SD

Mean±SD

Female age

33.61±5.22

33.07±5.68

0,39*

Male age

36.64±5.77

35.57±6.07

0,12*

BMI

23.95±3.72

24.29±4.22

0,46*

Duration of infertility

5.65±4.45

5.34±3.87

0,85‡

n

%

None

456

73.55%

Yes

164

26.45%

None

388

62.58%

1 attempt

128

20.65%

2 attempts

56

3 attempts

32

n

p

%

272

46.90%

0.00

366

63.10%

-

92

15.86%

0.28+

-p

54

9.31%

0.74+

5.16%

48

8.28%

0.44+

16

2.58%

20

3.45%

0.68+

516

83.23%

462

79.65%

-

1 attempt

60

9.68%

48

8.28%

0.88+

2 attempts

36

5.81%

49

8.45%

0.49+

8

1.29%

21

3.62%

0.36+

164

26.45%

152

26.21%

Low Ovarian Reserve

192

30.97%

164

28.28%

Tubal Factor

36

5.82%

40

6.90%

Endometrioma

40

6.45%

48

8.28%

Male Factor

176

28.40%

156

26.90%

Others

12

1.94%

20

3.45%

>4 attempts

na

None

FET attempts (n)

53.10%

re

IVF attempts (n)

308

9.03%

lP

ovaries

ro of

D3 Presence of polycystic

>3 attempts

ur

Unexplained Infertility

Jo

Etiologies of infertility

0.93+

*: Unpaired t-test , ‡: Mann-Whitney U test, +: Chi-square Test, Mean±SD: Mean±Standard Deviation, BMI: Body Mass Index, ET: Fresh Embryo Transfer, sFET: Selective Frozen Embryo Transfer

20

Table 2. Clinical Features of the ET and sFET Groups sFET Group

(n=620)

(n=580)

p

Mean±SD

6.08±2.62

6.32±2.72

0.44*

D3 Endometrial Thickness

Mean±SD

4.1±1.13

4.33±1.71

0.39*

Stimulation Duration

Mean±SD

10.12±1.84

10.48±1.95

0.10*

D3 FSH

Median (IQR)

6.86 (5.7-10)

7.28 (6-9.8)

0.54‡

D3 LH

Median (IQR)

7.3 (6-10.5)

7.7 (5.61-10.15)

0.89‡

D3 E2

Median (IQR)

41 (34-65)

43 (34.5-61.5)

0.95‡

hCG day E2

Median (IQR)

1596 (980-2086)

2359 (1249-3811)

0.00‡

hCG day P4

Median (IQR)

0.76 (0.48-0.98)

1.02 (0.73-1.56)

0.00‡

Oocytes collected (n)

Mean±SD

9.16±5.36

13.48±8.17

0.00‡

Mature oocytes (n)

Mean±SD

7.44±4.52

10.5±6.34

0.00‡

Fertilized oocytes (n)

Mean±SD

6.12±4.15

8.92±6.00

0.00‡

Mean±SD

1.61±0.51

1.83±0.46

0.00*

Mean±SD

10.2±1.47

10.35±1.44

0.39*

Transferred embryos (n)

lP

re

ro of

D3 AF

-p

Clinical Features

ET Group

Endometrial thickness on day of transfer

na

*: Unpaired t-test, ‡: Mann-Whitney U test Mean±SD: Mean±Standard Deviation, D3: Third day of the menstrual cycle, AF: Number of antral follicles <8 mm, P4: Progesterone, E2: Estradiol, ET: Fresh Embryo Transfer, sFET:

Jo

ur

Selective Frozen Embryo Transfer, hCG: Human Chorionic Gonadotropin

21

Table 3. Pregnancy Results of the ET and sFET Groups ET Group (n=620)

sFET Group (n=580)

P*

%

n

%

Pregnancy Positive

376

60.65

432

74.48

0.00+

Biochemical pregnancy

20

3.22

20

3.44

0.36+

Ectopic Pregnancy

4

1.06

0

0

0.28+

Clinical Pregnancy

352

56.77

412

71.04

0.00+

Abortion

76

12.25

68

11.73

0.48+

Live Birth

276

44.52

344

59.31

0.03+

Single

236

38.37

272

46.90

0.04+

Twin

40

6.15

72

12.41

0.03+

ro of

n

Jo

ur

na

lP

re

-p

+: Chi-square Test, ET: Fresh Embryo Transfer, sFET: Selective Frozen Embryo Transfer

22

Table 4. Factors Affected by Frozen-Thawed Embryo Transfer Univariate ß

OR

Multivariate p

ß

p

(95% CI)

0.90

0.41 (0.25-0.66)

0.00

0.02

0.98 (0.38-2.56)

0.96

Triggering Day E2

0.001

1 (1-1001)

0.00

0.00

1.00 (1-1)

0.00

Trigering Day P4

1.83

6.24 (3.37-11.56)

0.00

1.41

4.09 (1.93-8.66)

0.00

Oocytes collected (n)

0.09

1.1 (1.05-1.14)

0.00

0.09

1.10 (0.96-1.25)

0.18

Mature oocytes (n)

0.10

1.11 (1.06-1.16)

0.00

0.21

0.81 (0.66-1.00)

0.04

Fertilized oocytes (n)

0.11

1.12 (1.06-1.17)

0.00

0.09

1.09 (0.94-1.27)

0.25

Transferred Embryos (n)

0.93

2.54 (1.56-4.13)

Pregnancy Positive

0.67

0.53 (0.32-0.86)

Clinical Pregnancy

0.61

0.63 (0.39-0.95)

0.00

Live Birth

0.52

0.03

-p 0.00

1.40

4.07 (2.21-7.51)

0.00

0.00

0.24

0.79 (0.34-1.81)

0.57

0.86 (0.41-1.92)

0.41

1.22 (0.56-2.67)

0.61

re

1.68 (1.06-2.65)

ro of

PC Ovaries or PCOS

lP

(95% CI)

OR

0.35 0.20

P4: Progesterone E2: Estradiol, hCG: Human Chorionic Gonadotropin PC: Polycystic PCOS: polycystic ovary

Jo

ur

na

syndrome