It is a well-established fact that in women fertility decreases rapidly after age 40 and we at InVia Fertility Specialists therefore tend to treat this group of patients aggressively.
In younger patients, we will generally start treatment with three cycles of ovulation induction with clomiphene citrate and timed intrauterine inseminations (CC/IUI). In patients that fail to conceive with CC/IUI, the next step is either ovulation induction with gonadotropins and timed intrauterine inseminations (FSH/IUI) or in vitro fertilization (IVF).
Dr Reindollar and colleagues from Boston IVF (Fertil Steril 2010;94:888-899) have shown that FSH/IUI was of limited use in younger couples that failed to conceive with CC/IUI. They found the pregnancy rates were significantly higher when FSH/IUI was skipped and patients were treated instead with IVF.
In older patients, CC/IUI is believed to be ineffective. It is therefore common to skip this step and start directly with FSH/IUI for 3 cycles before proceeding with IVF. Is this really true?
But, what is really the optimal treatment for women greater that 40 years with unexplained infertility?
This very issue was addressed by Goldman et al. from Boston IVF; Dartmouth and Harvard Medical School (Fertil Steril 2014;101:1574-1581). They recruited couples with greater than 6 months of unexplained infertility and female partner aged 38–42 years.
Inclusion criteria were the following: at least one ovary and ipsilateral patent fallopian tube confirmed by hysterosalpingogram or laparoscopy; regular menstrual cycles of 21–45 days; and no pelvic pathology, ectopic pregnancy, or previous infertility treatment (except up to three cycles of clomiphene without IUI). Acceptable ovarian reserve, normal prolactin and thyroid- stimulating hormone levels and a body mass index (BMI) less than 38 in the woman, and a sperm concentration of greater than 15 million total motile sperm or greater than 5 million total motile sperm at reflex IUI preparation in her partner were required.
They conducted a three-arm randomized controlled trial (RCT) to evaluate treatment strategies for older infertile couples. Treatment began with two cycles of one of the following regimens: CC/IUI, FSH/IUI, or immediate IVF. Couples who did not become pregnant were treated with IVF, up to a study maximum of six IVF cycles. They randomized 154 couples to receive CC/IUI (n = 51), FSH/IUI (n = 52), or immediate IVF (n = 51); 140 (90.9%) couples initiated treatment.
The results were very interesting. The cumulative clinical pregnancy rates per couple after the first two cycles of CC/IUI, FSH/IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. After all treatments, 110 (71.4%) of 154 couples had conceived a clinically recognized pregnancy, and 46.1% had delivered at least one live-born baby; 84.2% of all live-born infants resulting from treatment were achieved via IVF. There were 36% fewer treatment cycles in the IVF arm compared with either COH/IUI arm, and the couples conceived a pregnancy leading to a live birth after fewer treatment cycles.
In this RCT of reproductively older couples with unexplained infertility, the clinical pregnancy rates in the immediate IVF arm were statistically significantly higher after two cycles of treatment than in the treatment arms that initiated therapy with either CC/IUI or FSH/IUI. In addition, when comparing the number of treatment cycles per live birth for each of the arms, a statistically significant difference existed with fewer treatment cycles per live birth in the immediate IVF arm. At the conclusion of the trial, 46% of couples delivered a baby, the majority of whom were conceived using IVF.
The trial data support the use of CC/IUI for such treatment; it is similar in efficacy to FSH/IUI and easier and less costly for the patients.
They conclude that for women greater than 40 years old and unexplained infertility, the most successful treatment is immediate IVF. About half will have a live birth (more than 80% of these will be singletons). For couples who do not want immediate IVF, their data support the use of CC/IUI rather than FSH/ IUI, given the comparable success rates. However, for couples initiating treatment with CC/IUI who then move on to IVF, the majority of their infants will be conceived by IVF and, on average, they will undergo more treatment cycles than patients who elect immediate IVF.
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