In vitro fertilization (IVF) has brought children to millions who otherwise had difficulty conceiving so it should be a happy time.   Yet over 20% of women who undergo IVF report symptoms of depression.

The belief has been that the common denominator in women who undergo IVF - hormone therapy - is the culprit, but new Tel Aviv University shows that other factors have a large influence in who gets depressed and why and resolving those issues will make the success of the IVF greater.

Different hormonal states are  triggers for depression during IVF, both for long- and short-term protocols.  In the long-term IVF protocol, explains Dr. Miki Bloch of Tel Aviv University's Sackler Faculty of Medicine, women receive injections which block ovulation, resulting in a sharp decline in estrogen and progesterone levels. This state continues for a two-week period before the patient is injected with hormones to stimulate ovulation, at which point the eggs are harvested and fertilized before being replanted into the womb. The short-term IVF protocol, on the other hand, does not include the initial two-week period of induction of a low hormonal state.

Some gynaecologists believe that depression is more likely when a woman undergoes long-term IVF therapy because of those first two weeks of hormonal repression. But Dr. Bloch's research has demonstrated that the difference between the two different procedures is negligible ― depression and anxiety rates for women who undergo the long protocol and those who undergo the short are exactly the same.

Dr. Bloch and his fellow researchers conducted a random assignment study, in which 108 women who came to the Sourasky Medical Center for IVF were randomly assigned to either the long- or short-term protocol. They were given questionnaires and interviews at the start of the therapy and at four other points during the IVF treatment.

The results, says Dr. Bloch, show consistently increasing depression rates among patients in both groups, irrespective of which protocol they underwent. The first two weeks of hormonal repression, he explains, thus have no impact on whether a woman experiences depression during IVF. "Once the patient begins ovulating, her estrogen rises to high levels. Then, after the ovum is replanted in her uterus, there is a precipitous drop in these hormonal levels," he explains. It's the severity of the estrogen drop, a feature of both protocols, that was found to affect the patient's emotional state.

Whatever the specific effect of hormones, during their study Dr. Bloch and his fellow researchers discovered that the stress and anxiety experienced during the treatment has a significant impact on patient depression rates. When compared to a "normal" population, women undergoing IVF experience very high levels of anxiety and depression even before the treatment begins. As the protocol advances, explains Dr. Bloch, women experience increased anxiety about the success of the implantation. 

Women who have a previous history of anxiety or depression disorders before the IVF treatment are even more susceptible, he says. This is likely due to the fact that these women are more emotionally vulnerable to the toll of the IVF process rather then increased reactivity to changing hormonal levels, Dr. Bloch says.

Choosing the right protocol

When it comes to depression rates, the type of protocol a patient undergoes, whether short-term or long-term, has no impact, Dr. Bloch concluded. The combination of the stress surrounding the treatment, a personal history of psychiatric disorders, and a sharp decline in estrogen levels are the main contributing factors towards depression during IVF therapy. While doctors should look at their patient's individual needs when deciding on an IVF protocol, the current report suggests the type of protocol per se is not an important factor in the induction of depression.

Citation: Miki Bloch, Foad Azem, Inbar Aharonov, Irit Ben Avi, et al., 'GnRH-agonist induced depressive and anxiety symptoms during in vitro fertilization–embryo transfer cycles', Fertility and Sterility doi:10.1016/j.fertnstert.2010.07.1073