Effects of E2, P4 and LH Levels on the Day of Transfer and Endometrial Cavity Thickness on Implantation Success in Patients With Frozen-thawed Embryo Transfer Cycle
Condition: Infertility; IVF; Progesterone
MeSH terms: Infertility
Study type: Interventional

Summary: 
      Thanks to recent advances in clinical practice and laboratory, embryo cryopreservation has
      become the first-line procedure in assisted reproductive technology. Embryo freezing process;
      Prevention of ovarian hyperstimulation syndrome is becoming an accepted practice for a
      growing number of indications, including preimplantation genetic testing (PGT), late
      follicular phase progesterone elevation, and embryo-endometrial asynchrony. Progesterone;
      plays a key role in the preparation of the endometrial cavity for embryo attachment.
      Supplementary progesterone preparations can be used to prevent luteal phase defects and
      provide progesterone support during cycle preparations for frozen-thawed embryo transfer. Our
      aim in this study is to show the effect of serum progesterone level on pregnancy outcomes on
      the day of embryo transfer.
    

Detailed description: 
      This prospective cohort study was conducted at IVF center of Bezmialem University Hospital
      and Acibadem Health Group between Februrary 2021-September 2021. A total of 234 programmed
      frozen ultrasound-guided ETs, performed by two physicians (P.O. and C.F.) were included. The
      study protocol was approved by the Ethical Committee of the Medical Faculty of Bezmialem
      University. Written informed consent was obtained from all patients. Inclusion criteria were
      patients underwent IVF between 18 and 41 years old. Exclusion criteria were patients with
      uncorrected intracavitary structural uterine anomalies including unicornuate, bicornuate or
      didelphic uterus, recurrent miscarriage, presence of hydrosalpinx, and cycle cancelation.
      Those undergoing corrective uterine anomalies such as uterine septum, submucosal fibroids,
      and endometrial polyps were not excluded.

      Data collected included age, duration of infertility, type of infertility, indication of IVF,
      smokers (%),number of previous attempts, serum estradiol (pg/ml), LH (IU/l), progesterone
      level (ng/ml) and endometrial thickness (mm) prior to progesterone introduction and on embryo
      transfer day, number of embryos transferred, embryo stage at transfer (Day 3/blastocyst) (%),
      control progesterone level on post-embryo transfer (ng/ml), the air bubbles (C) at 1 and 60
      minutes after embryo transfer,miscarriage, clinical pregnancy rate (the presence of fetal
      heartbeat visualized by transvaginal ultrasound examination) and ongoing pregnancy rate at 12
      weeks of amenorrhea.

      Embryo Selection and ET Vitrification on Day 3 or at the blastocyst stage and warming were
      performed by using commercial vitrification kits according to the manufacturer's
      instructions. All ETs were performed by two experienced operator (P.O. and C.F.) with Wallace
      catheter (Smiths Medical International Ltd.) using after-load transfer technique under
      transabdominal ultrasound guidance with moderately full bladder, without any anesthesia or
      sedation. The highest quality embryos according to morphology and cleavage criteria were
      selected for transfer. After the procedure, the patient was kept supine for approximately 60
      minutes. Ultrasonography were carried out at 1 and 60 minutes after ET to record the embryo
      flash position assessed by measuring the distance between the air bubble and the uterine
      fundus in the coronal image. The embryo flash movement/migration was assessed by measuring
      the change of the embryo flash position at 60 minutes after ET. When more than one air bubble
      was seen, the closest one to uterine fundus was used for the measurements. Investigators
      measured the distance from the lead portion of the air bubble to the uterine fundus.

      Endometrial preparation and progesterone support Down-regulation with OCS and a GnRH agonist
      (Lucrin® 3.75 mg IM, single dose, Ipsen Pharma, Barcelona, Spain) was first done for all
      patients at the previous cycle and then HRT was used for endometrial preparation at next
      cycle. Transvaginal ultrasound was performed and serum estradiol, LH and progesterone levels
      were also measured on the second or third day of menstrual cycle. HRT was started with oral
      estradiol valerate in a stepwise manner up to 8 mg/day. After 14 days on estrogen
      supplementation, endometrial thickness was measured by a vaginal 2D ultrasound and serum
      estradiol, LH and progesterone levels were also measured. If endometrial thickness was >7 mm
      with a triple layer pattern and quiescent ovaries, serum E2 was >100 pg/ml and the serum P
      level was <1.5 ng/ml, progesterone supplementation was initiated by the use of 100 mg of a
      vaginal progesterone tablet two times daily (Lutinus) plus 250 mg of intramuscular
      hydroxyprogesterone caproate in oil weekly twice as luteal phase support (referred to as day
      0 of progesterone administration). Embryo transfer was performed on the day 3 for Day 3
      embryos and on day 5 for blastocysts. The blood samples were taken for all patients to
      measure serum progesterone and estradiol levels at the day of ET. If serum progesterone
      levels were <10 ng/ml at the day of embryo transfer 25 mg/d of SC progesterone daily
      (prolutex) were given to patients and a the blood sample was taken 2 days later to check
      serum progesterone levels. Serum quantitative beta- hCG levels were obtained at 12 days after
      ET. Progesterone supplementation as luteal phase support was continued at the same dose until
      10-12 gestational weeks of viable pregnancies and discontinued if no pregnancy. Oral E2 was
      discontinued after the presence of fetal heartbeat visualized by transvaginal ultrasound
      examination.
    

Intervention name(s): Normal Progesterone group; Low Progesterone group
Intervention type(s): Other; Other
Intervention description(s): Progesteron supplementation was initiated by the use of 100 mg of a vaginal progesterone tablet two times daily (Lutinus, Ferring Pharmaceuticals) plus 250 mg of intramuscular hydroxyprogesterone caproate in oil twice a week (IMHPC) as luteal phase support (referred to as day 0 of progesterone administration).; Progesterone level <10 ng/mL on ET day. If serum progesterone levels were <10 ng/ml at ET day, 25 mg/d of SC progesterone daily (Prolutex) was given to patients and ET was performed on the same day and the blood sample was taken 2 days later to check serum progesterone levels.
Intervention MeSH terms: Progesterone
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: progesterone; infertility; estradiol