Introduction
I
VF-ICSI is performed widely in the world and implantation is essential as much as follicular development for a successful treatment. Especially, implantation is necessary for a successful pregnancy and requires a healthy blastocyst apposition and endometrial receptivity (1, 2).
Many cytokines (IL-6, IL-8, and TNFα), matrix metalloproteinases (MMP), and molecules characterizing early implantation have been discovered (3, 4). Barash
et al reported that endometrial biopsy taken spontaneous cycle that preceded IVF improves the IVF-ICSI outcomes such as implantation rate, clinical pregnancy rate, and live birth rate (5). They claimed that the cause of implantation improvement was secondary modifications due to an injury-induced inflammatory reaction. Despite considerable advances in assisted reproductive techniques (ART), management of the patients who had recurrent IVF failure is still a challenge.
The aim of this study was to detect the efficacy of the endometrial biopsy performed in the nontransfer cycle proceeding the IVF-ICSI cycle.
Materials and methods
This is a retrospective cross-sectional study. The patient characteristics (basal hormone levels, duration of infertility, number of attempt, body mass index, antral follicle count, and age) were analyzed, retrospectively. The groups were homogen in terms of these parameters. Inclusion criteria were at least one previous failed IVF-ICSI cycle with a fresh embryo, having good response in the previous IVF cycle, and less than or equal to 37 years old.
The cases in which testicular sperm extraction (TESE) procedures were performed were not included the study. Spermogram values of the patients were in normal ranges. Male factor patients were excluded from the study. The patients whose body mass index were (BMI) >30 were not included into the study. Standard IVF-ICSI procedure was performed for all of the patients. The patients were randomized to two groups. All women were assessed with baseline day 3 follicle stimulating hormone (FSH), antral follicle count (AFC), estradiole (E
2) level, and hysteroscopy (H/S) on the 21st day of the previous cycle. Day 21 of the cycle has been assessed by ultrasonography and estradiole (E
2) level.
The patients in the study group underwent endometrial sampling once, with a biopsy catheter (Pipelle; Gynetics Medical Products, Hamont Achel, Belgium) on the 21
st day of the nontransfer cycle. The Pipelle was moved up and down into the uterine cavity. All the women were given Indomethacine 25mg 30-60 minutes prior the procedure. Ciprofloxacin 500 mg was given twice daily for 7 days after the biopsy. Contraception was suggested to women in the nontransfer cycle.
In long protocol cases, pituitary was down-regulated with Leuprolide acetate (Lucrin ® daily 0.25 mg Abbott, USA). Lucrin was given for at least 10 day starting on the 21
st day of the menstrual cycles. On the 2nd day of menstruation, transvaginal ultrasonography (TV USG) and serum E
2 level were monitorized to show the suppression. Controlled ovarian stimulation (COS) was performed with FSH starting on cycle day 3. Highly purified-urinary FSH (Fostimon HP ® 75 IBSA, Switzerland) was administered. Average FSH starting dose was 450 iu and the dose was individually adjusted according to the previous treatment cycles, body mass index (BMI), and age.
Pituitary was down-regulated with Cetrorelix (Cetrotide® 0.25 Merck-Serono, Switzerland) in the antagonist protocol starting on the sixth or seventh day of the cycle according to the follicular growth (when the leading follicle reached to 13-14 mm) and E
2 level (when the level exceeded 600-800 pg/ml). Cetrorelix was continued until the day of hCG. COS was performed with either r FSH or HP-u FSH starting on cycle day 3. Age, body mass index (BMI), and response to the former treatment were used to detect the beginning FSH dose. Average FSH starting dose was 225 IU.
Ovulation induction was monitorized by using E
2 measurement and TV USG. Human chorionic gonadothropin (Pregnyl® 5000 IU × 2, Schering-Plough, USA) was administered when the dominant follicle reaches 17 mm. Oocytes were retrieved by TV USG- guided needle aspiration. IVF- ICSI was performed in all cases. Embryos were classified according to percentage of fragmentation and blastomere appearances as type I, II, III or IV on 1
st, 3
rd and 5
th days. Up to two embryos were transferred into the uterine cavity on day 2, 3 or 5. Luteal phase was supported by progesterone administration (Crinone %8 vaginal gel ® Merck-Serono, Switzerland). Progesterone was given during 12 days after oocyte retrieval.
Progesteron support was maintained until the 12
th gestational week in the pregnancy cases. Implantation failure was defined as the failure of embryo to achieve pregnancy. Fertilization rate was determined as the number of embryos (