Test-tube baby blues
Many women embarking on IVF become depressed when it doesn't work, but the medical solution-antidepressants-is linked to problem pregnancies and even birth defects
Having trouble getting or staying pregnant is highly stressful, and probably why more than one in 10 women undergoing fertility treatment takes a drug for depression. But this practice may simply be making matters worse.
New evidence shows that women taking antidepressants like Prozac while trying to get pregnant face increased risks of losing the baby, giving birth early and having babies with physical or mental abnormalities, including autism.
American scientists who recently reviewed all published studies of the effects of taking antidepressants during pregnancy discovered that pregnant women taking selective serotonin re-uptake inhibitors (SSRIs), which include drugs like Prozac and Paxil, face increased risks of miscarriage, preterm birth defects, newborn behavioural syndrome, persistent pulmonary hypertension of the newborn and even brain damage, leading to conditions such as autism (Hum Reprod, 2012; doi: 10.1093/humrep/des383).
Their report raises serious concerns because of the large number of mothers and babies potentially affected. At least one in every one hundred babies born in the US is the result of an in vitro fertilization (IVF) cycle, a situation that itself causes women to become depressed because of the low success rates.
"Most women will report symptoms of depression during infertility treatment, especially following unsuccessful treatment cycles," write the study's authors.
Antidepressant use has in-creased by 400 per cent in the last two decades, making it the most commonly prescribed class of drugs in the US for those between ages 18 and 44-the usual childbearing years.
Lead author Alice Domar, a PhD in obstetrics and gynaecology at Beth Israel Deaconess Medical Center, sums up the review's stark conclusion: "First, there is a clear and concerning evidence of risk with the use of SSRI antidepressants by pregnant women, evidence that these drugs lead to worsened pregnancy outcomes. Second, there is no evidence of benefit, no evidence that these drugs lead to better outcomes for mothers and babies."
In fact, SSRIs may actually lower your chances of getting pregnant, or producing a live or healthy baby if you are presently undergoing fertility treatment. As numerous studies demonstrate, women taking antidepressants increase their risk of miscarriage.
Furthermore, more than 30 of the reviewed studies showed that women taking SSRIs are more likely to give birth to babies prematurely, which may adversely affect their future health.
"Babies born before 37 weeks are at risk for many short- and long-term health problems," said Adam Urato, chairman of obstetrics and gynaecology at MetroWest Medical Center and a Maternal Fetal Medicine specialist at Tufts Medical Center.
Pregnant women who take antidepressants also risk giving birth to a child with congenital abnormalities. The link has already been so well established between taking the drug Paxil (paroxetine) and having a baby with heart defects that the US Food and Drug Administration (FDA) requested that GlaxoSmithKline, the drug's manufacturer, spell it out as a clear risk in its datasheets.
Other evidence links taking SSRIs during pregnancy with a two-and-a-half times higher risk of producing a baby with anencephaly (where the skull doesn't develop properly and the brain is missing one or both of its hemispheres) and other birth defects of the skull and nervous system (N Engl J Med, 2007; 356; 2684-92). Babies exposed long-term to SSRIs are also more likely to be born with a birth weight below the 10th percentile, which can lead to breathing problems or delays in motor development.
Domar and her colleagues found one study from 2006 showing that babies exposed to SSRIs during pregnancy carry a 30-per-cent increased risk of 'newborn behavioral syndrome', an umbrella term for babies who cry constantly, have difficulty feeding, seldom settle and, in extreme cases, suffer seizures or breathing difficulties. Other research carried out by Kaiser Permanente found that women taking antidepressants during pregnancy, particularly within the first trimester, double their risk of giving birth to a child with a disorder along the autistic spectrum.
SSRI use can also make for a problematic pregnancy, parti-cularly if continued beyond the first trimester. The researchers found evidence the drugs increased the risk of pregnancy-induced hypertension (high blood pressure) and even preeclampsia which, if left untreated, can lead to the life-threatening convulsions and coma of eclampsia-the condition that claimed the life of Lady Sybil in the TV series Downton Abbey.
Despite all of this extensive research, the authors, from Beth Israel Deaconess Medical Center, Tufts Medical Center and MetroWest Medical Center, all in Massachusetts, could find no evidence that the drugs did any good. Antidepressant use did not improve the outcome of pregnancy in any way or indeed successfully tackle the depression experienced by women trying to get pregnant.
In fact, many of the studies they reviewed found SSRIs to be no more effective than placebos in treating depression. The authors put it even more strongly: "There is little evidence of benefit from the antidepressants prescribed for the majority of women of childbearing age", but "enough evidence to strongly recommend that great caution be exercised before prescribing SSRI antidepressants to women who are pregnant or who are attempting to get pregnant, whether or not they are undergoing infertility treatment," says Domar.
The research team did find better and safer options for pregnant women suffering from depression. Cognitive behavioural therapy works as well as antidepressant drugs for mild-to-moderate depression and even severe depression, they note. According to a 2008 study, 79 per cent of women undergoing fertility treatment suffering from depression reported a significant decrease in symptoms following cognitive behavioural therapy (CBT) compared with just 50 per cent of women taking the drugs.
Depressing your sex life
Trying to have a baby repeatedly without success is enough to get any woman depressed, but there's another reason why IVF causes depression, and that's the effect it has on your sex life.
A new study from Indiana University found that infertility treatment, with all the essential state-of-the-art pharmaceuticals and equipment, has a negative impact on a woman's sexual relationship with her partner.
"With assisted reproductive technologies, couples often report that they feel like a science experiment," said Nicole Smith, the doctoral student at the Center for Sexual Health Promotion at Indiana University School of Public Health who is conducting the study (with a partner from Indiana University Maurer School of Law).
"Hormones are administered and sex has to be planned and timed. It can become stressful and is often very unromantic and regimented; relationships are known to suffer during the process."
One of the first in the US to examine women's sexual experiences during assisted reproduction, the study asked women to complete a questionnaire about their sex lives, then interviewed a variety of women, including women using IVF to conceive as well as 70 professionals working in some way with assisted reproduction. Compared with women conceiving naturally, those women undergoing IVF reported significantly less sexual desire, less interest in sexual activity and lower satisfaction with their sexual relationship.
The women also complained of having more difficulty with orgasm and more problems with vaginal pain and dryness. These problems only intensified as a couple carried on with IVF and arose regardless of whether the couple's infertility issues were related to the man or the woman.
Bedroom blues? Look to the drugs
When women have sexual difficulties from the rigours of IVF, it's not simply due to the mental or emotional impact of sex on demand rather than for pleasure, but also because of the drugs used in the procedures. The hormonal treatments commonly used for assisted reproduction, which essentially take over a woman's monthly cycle to control when she ovulates, also affect women's sexual experiences and pain.
Gonadotrophin-releasing hormone (GnRH) analogues and pituitary agonists such as nafarelin, buserelin and goserelin, used to halt the natural menstrual cycle and block the natural release of hormones regulating the monthly cycle, lead to low levels of female hormones like oestradiol, and are known to cause hot flushes, vaginal dryness and mood swings.
Other drugs such as cetrorelix and ganirelix, which are gonadotrophin-releasing hormone antagonists used to stop ovulation until the eggs are ready to be collected for the IVF cycle, cause headaches, dizziness and a general sense of unwellness.
vol 23 no 9 December 2012