OPEN Research Support

Louise Svenstrup
Fertility Center, Department of Gynaecology and Obstetrics, Odense University Hospital

Projekt styring
Projekt status    Sampling ongoing
Data indsamlingsdatoer
Start 01.09.2014  
Slut 28.02.2017  

Assisted reproduction and the early luteal phase

Short summary

Three prospective randomized trials with women in fertility treatment undergoing IVF or spontaneous IUI. Eight to nine blood samples are taken during the early luteal phase.

All IVF patients are in GnRH antagonist protocol.  Study I: Normal responders are randomized to have different dose of ovulation induction. Study II: High responders are trigged with Suprefact and receive luteal phase support as one dose hCG or divided hCG dose. Study III: One corpus luteum in spontaneous IUI after LH-test versus ovulation induction.

For further information please see under rationale.



Assisted reproduction technology (ART) contributes significantly to the birth cohort in Denmark. In 2012 it was estimated that approximately 8.8% of the birth cohort derived from ART. In total, the live birth rate deriving from IVF/ICSI was estimated to be 5.5%. The IVF treatment can be subdivided into three phases: a stimulation phase, an in vitro phase and in utero phase (the luteal phase). The luteal phase after all stimulated IVF cycles is abnormal, due to the multi follicular ovarian development caused by exogenous hyperstimulation. Supra physiological levels of steroids (estradiol and progesterone) exert a negative feedback on the endogenous LH production, resulting in low LH levels during the luteal phase. As luteal LH plays a significant role for corpus luteum function and thus the subsequent implantation and pregnancy, luteal phase support is mandatory after ovarian stimulation especially during the peri-implantation period. Consequently, a further optimization of the current luteal phase support might carry the potential to further increase the number of successful implantations and, thus, the reproductive outcome after ART. 


Study I: To explore the hormone profile, particularly of progesterone in the early luteal phase in relation to three different doses of hCG for ovulation trigger. Additionally, to correlate the estradiol level, the follicular number, the number of follicles aspirated and the total number of oocytes retrieved per patient to progesterone production and if possible then determine progesterone production per corpus luteum.

Study II: To investigate the hormone profile in high responder patients, to identify if separation of luteal phase hCG support is a more optimal luteal support than one dose of hCG after oocyte pickup.

Study III: To explore the endogenous progesterone production 24 hours after ovulation and seven days later in a single corpus luteum in a natural cycle compared to the progesterone output after hCG trigger.


Study I: In total 100 Women undergoing GnRH antagonist co-treatment for IVF/ICSI are randomized into 4 groups using different doses of hCG for ovulation trigger: 5000 IU, 10.000 IU and 6500 IU. The luteal phase support will consist of 17-?-hydroxy-progesterone in order to differentiate from the endogenous progesterone production. A control group will have 6500 IU and standard progesterone. Oocyte pickup, embryo, culture and embryo transfer will be performed according to normal standards. During the luteal phase eight blood samples will be collected.  

Study II: 69 high responder women with between 12 and 25 follicles in antagonist IVF/ICSI treatment are randomized into three groups. In two groups Suprefact is used for ovulation trigger. In one group luteal support consists of a 1500 IU hCG bolus after oocyte pickup, and in the other group hCG is divided into 1000 IU on oocyte pickup day followed by 500 IU on the fifth dag. The control group will have Ovitrelle for ovulation trigger. All three groups will receive a standard luteal phase support. Like in study one, oocyte pickup, embryo, culture and embryo transfer will be performed according to normal standards and eight blood samples will be collected during the luteal phase.   

Study III: Ten women in natural IUI cycle are randomized into two groups. One group in a total natural cycle is compared with another group having 6500 UI Ovitrelle for ovulation induction. Within 24 hours after ovulation, a total of eight blood samples will be collected as well as one blood sample collected one the seventh day after ovulation.

Description of the cohort

18-40 years old women in fertility treatment with BMI between 18 and 35kg/m² and normal FSH, LH, estradiol, prolactin and TSH.

Data and biological material

The biobank contains three Sarstedt tubs with 1 ml serum from every blood sample from each patient.

Blood samples:

Study I and II: Day of ovulation trigger (or - 1), day of OPU, ET dag (OPU + 2), OPU + 4, OPU + 6, OPU + 8, OPU + 10 and on the day of the pregnancy test.

Study III: Seven blood samples on the ovulation day, once every second hour, the next day in the morning and one seven days after ovulation.

Clinical data on all patients: Age, BMI, blood pressure, allergies, current or active clinical important diseases, medications, alcohol and tobacco habits. Menstrual cycles, previously pregnancies and deliveries. Former fertility treatment, years of infertility and infertility diagnose. Dose and type of medication for stimulation, total length of stimulations phase. Ultrasound measurement: Follicle count and size, endometrial thickness. Total number of follicles aspirated and the total number of oocytes retrieved per patient. Transferred and frozen oocytes per patients. Fertility methods (IVF or ICSI), semen source, result of the pregnancy test and the pregnancy scan.

Collaborating researchers and departments

Fertility Clinic, Skive Regional Hospital

  • Professor and Senior consultant Peter Humaidan, DMSc

Fertility Clinic, Odense University Hospital

  • Professor and senior consultant Jens Fedder, PhD
  • Chief biologist Karin Erb

Laboratory of Reproductive Biology, University Hospital Copenhagen, Rigshospitalet

  • Professor Claus Yding Andersen, DMSc

NordicInfu Care, Sweden