Study Information ProFET

Treatment with progesterone during frozen embryo transfer after IVF, in menstrual cycle with natural ovulation 

The study is called "ProFET," where Pro stands for Progesterone—the medication given as follow-up treatment—and FET stands for Frozen Embryo Transfer. 

Information for research participants 
We would like to ask if you want to participate in a research project. This document provides information about the project and what participation means. 

What is the project and why do you want me to participate? 
Within IVF treatment (in vitro fertilization), transfer of embryos thawed after freezing has become increasingly common. Frozen embryo transfer now accounts for 46% of IVF treatments in Sweden (www.qivf.se, Annual Report 2020). The increased use of frozen embryo transfer is due to significantly improved results following the introduction of new freezing and culture methods. 

The corpus luteum that develops in the ovary after ovulation is important to support an early pregnancy. For this reason, extra corpus luteum hormone, progesterone, is given after embryo transfer in menstrual cycles where the woman has not ovulated. Progesterone treatment is likewise given to all patients undergoing IVF stimulation and embryo transfer in so-called fresh IVF cycles, as hormone production is suppressed in these treatments. 

For frozen embryo transfer in a natural menstrual cycle with spontaneous ovulation, it is currently unknown whether progesterone treatment improves the chances of pregnancy and childbirth. Still, this treatment is used at several clinics, which may be unnecessary and burdensome for patients. 

You are invited to participate because you are eligible for IVF with frozen embryo transfer in a natural cycle. You are between 18–43 years old, have a BMI (body mass index) between 18.5–35 kg/m2, a regular menstrual cycle, and understand Swedish, English, or Arabic. 

The research sponsor is the Reproductive Medicine Unit at Sahlgrenska University Hospital. 

How does the study work? 
You are in contact with a doctor or midwife/nurse before your frozen embryo transfer. If you meet the criteria and wish to participate, you submit written consent to the clinic or give digital consent via 1177. 

When the ovulation test turns positive, you contact the clinic following regular procedures and schedule the frozen embryo transfer. You will be randomly assigned by the responsible study doctor/midwife/nurse to one of three study groups: 
a) Frozen embryo transfer without follow-up treatment 
b) Vaginal progesterone tablet three times daily for three weeks 
c) Vaginal progesterone tablet three times daily for seven weeks 

It is not possible to choose a group; the allocation is done by an independent data system. If you belong to one of the progesterone groups, you start progesterone treatment three days after the positive ovulation test. The medication can be collected at the clinic or dispensed via e-prescription if you prefer to pick it up at any pharmacy. 

When practical, a blood test will be taken three days after the ovulation test before starting progesterone treatment. This blood test is also taken if you are in the no-progesterone group. The blood sample is about 5 ml, taken from the crook of the arm, and is analyzed for progesterone levels (S-progesterone) before the frozen transfer. Samples will be stored coded and frozen in a protected biobank in Gothenburg and analyzed after the study ends. 

During the frozen transfer visit, you will receive more medication if in groups b) or c). You will receive a questionnaire to note any side effects during treatment. This questionnaire will also be given to those not receiving medication. 

Pregnancy tests are done at home (urine test) following routine instructions always given after frozen embryo transfer. Phone contact will be maintained with the study nurse/doctor regarding results: 

Participation includes filling in questionnaires about symptoms potentially linked to the medication or other causes. You may need to take vaginal tablets three times daily for three or seven weeks and provide one blood sample. We will collect data on your pregnancy and delivery from medical records, as well as the baby’s condition from child health records. Data may also be gathered from national quality registries and Statistics Sweden. 

Possible consequences and risks of participation 
The treatment poses no risk unless you have hypersensitivity to the medication or a condition where it should not be given. No patient with such conditions will be allowed to participate. Participation involves no discomfort or pain. Some patients find the progesterone tablet sticky. There are no known long-term harmful effects from vaginal progesterone treatment. 

If you have questions, you can contact the project leaders via the study nurse during office hours. For urgent gynecological issues outside office hours, contact a gynecological emergency clinic. If you become ill otherwise, are hospitalized, or on sick leave, report this to the study nurse or responsible doctor, as all illnesses during a study must be reported according to regulations.