COGI discussion on luteal phase support
How can the Luteal phase be supported?
Luteal phase support during IVF/ICSI cycles was the topic of several debates at the COGI conference in Paris. Due to the nature of the conference, the focus was solely on the developments of assisted medical treatment and procedures for infertile couples.
During an IVF/ICSI cycle, the woman takes medication which cause her to secrete? lower levels of the LH? hormone?. This is known to have an effect on progesterone? and oestradiol levels and reduce the chance of pregnancy. This is why most women undergoing IVF/ICSI receive progesterone supplements to support the luteal phase.
Which protocol is best?
Dr DeVos reported that the In vitro maturation success rate correlated very well with the thickness of the endometrium?. McGill fertility centre has a unique approach, adapting the progesterone and oestradiol level to match the thickness of the endometrium at the time of egg? retrieval. Many centres were interested in this approach which had shown some good results.
How is it best to take progesterone?
Dr Milton Long surveyed IVF specialists to see which method of administration was the most commonly used. He found the majority of specialists use progesterone alone (no estrogen) to support the luteal phase during an IVF cycle. And we were surprised to learn that even though there is no evidence that taking progesterone for more than three weeks has any positive effect on pregnancy rate, many still recommended taking it for 10 – 12 weeks!
There are some advances in the area of progesterone supplementation, and Dr de Zigler presented new data indicating that we may soon have a subcutaneous progesterone supplement (injection) which could be less intrusive than the current vaginal route. There is however no improvement in pregnancy rate compared to the vaginal cream or pessaries and some women may not be comfortable injecting themselves.
The reason why oral progesterone is not recommended by most specialists is due to the metabolism of the hormone (conversion rate) leading to it's reduced activity. This is why it leads to a lower implantation?/pregnancy rate and a higher miscarriage rate when the progesterone is taken orally. The ASRM (American Society of Reproductive Medicine) recommended vaginal or Intra-Muscular injections, at the discretion of the doctor.
What are the risks involved with the progesterone treatment?
There has been a report of higher risk of hypospadia (Hypospadia is a male birth defect in which the opening urethra develops abnormally), however this has not be confirmed and we have not observed a general increase in this condition in the population level (which would be the case since IVF is now such a common procedure and progesterone is given in the majority of cycles).
What is the effect of progesterone on recurrent miscarriage?
Dr Pal led the discussion of luteal phase support on the topic of recurrent miscarriage risk. He described the many treatment options, highlighting the lack of solid evidence for many of them. For example, during the same year, two teams looked at low dose heparin to help reduce the risk of miscarriage. One concluded that it helped and the other one concluded that it made no difference (Qublan 2008 and Urman 2008). Were patients selected differently? And could this explain the difference in results?
The actual effect on recurrent miscarriage is still actively debated. But most fertility specialists agree that in the absence of clear risk, the potential benefit means that it is worth recommending progesterone to their patients.
Several experts discussed the use of progesterone to help reduce the risks of recurrent miscarriages for women with immunology disorders. They were generally in favour, however the exact mechanism of action of progesterone on the immune system is still unknown.
Dr Frydman, a French IVF specialist, challenged the audience to think about the endometrium (the lining of the womb?) when trying to understand repetitive implantation failure for IVF and IVM, in particular for PCOS patients. During these “treated cycles” the endometrium needs to be condsidered receptive to a potential pregnancy.
Is there evidence that progesterone can be useful to support the luteal phase in natural cycles?
Small studies have concluded that progesterone was not helpful in natural cycles. Unfortunately there is little information on how these patients were selected for this treatment. Further studies are required for the use of progesterone in natural cycles because the treatment of women with short luteal phases varies greatly across Europe.
