As The Clock Winds Down

Posted by on Jul 8, 2014 in IVF
As The Clock Winds Down

The importance of this criterion cannot be overstated, because a leading cause of infertility in women 38 and over is a decreased ovarian reserve.  With this factor in mind, it was predicted that the results obtained from this study would be better than if the same study was done for women with a reduced ovarian reserve, where the success rates would likely be less.

PICKING SIDES

The study was a randomized trail whereby 154 couples were randomly assigned to one of three treatment groups. The treatment groups consisted of 1. Clomiphene and intrauterine insemination(IUI)  (100 mg/day X 5 days starting between days 3-5, monitored either at home with LH timing or by ultrasound with HCG triggered ovulation); 2. FSH and IUI (starting on day 3 with 300 IU of FSH for three days and then adjusted based upon monitoring);  3.IVF ( oral contraceptives follow by a microdose protocol using 300 IU FSH in the morning and 150 hMG in the evening.)  If a patient did not conceive with two cycles of the initial treatment then they underwent IVF until 6 cycles had been accomplished with both fresh and frozen embryo transfers counting as a cycle.  The primary endpoint of the study was the clinical pregnancy rate after two cycles of treatment.  Clinical pregnancy was defined as a gestational sac seen on ultrasound.

The following results were recorded after the first two cycles of treatment:  Protocol #1 – CC/IUI = 21.6%; Protocol #2 – FSH/IUI = 17.3%; Protocol #3 – IVF= 49.0%.  This clearly demonstrated a statistically different result for the IVF protocol.  The live birth rates were also different amongst the groups, reflecting a similar trend : Protocol #1 –  CC/IUI = 15.7%; Protocol #2 – FSH/IUI= 13.5%; Protocol #3 – IVF= 31.4%. All of the patients not conceiving using either the CC/IUI or the FSH/IUI moved on to IVF where 35/99 (35.4%) couples conceived a pregnancy leading to a live birth.   If you add together all couples starting the study, 110/154 (71.4%) conceived a clinical pregnancy BUT only 71/154 (46.1%) delivered a live- born child. Interestingly, 14 of the live births were conceived when no treatment was given for a 9.1% treatment- independent pregnancy rate. Furthermore, of the remaining live births, 48/57 (84%) were conceived through the use of IVF.  Finally, for those patients who delivered a child, the average number of cycles of treatment was: Protocol #1 – CC/IUI = 3.4; Protocol #2 – FSH-IUI=3.3; Protocol #3 – IVF=1.9.

The importance of this criterion cannot be overstated, because a leading cause of infertility in women 38 and over is a decreased ovarian reserve.  With this factor in mind, it was predicted that the results obtained from this study would be better than if the same study was done for women with a reduced ovarian reserve, where the success rates would likely be less.

DETERMINING A ‘WINNER’

The conclusion reached by the authors was as follows: “A randomized controlled trial in older women with unexplained infertility to compare treatment initiated with two cycles of controlled ovarian hyperstimulation/ IUI versus immediate IVF demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group.” [Fertil Steril 2014: 101; 1574-81]

From a practical standpoint, one other point from this study is that FSH/IUI does not offer a superior pregnancy rate than clomiphene/IUI. Thus initiating treatment with clomiphene and then moving to IVF would be one option for women faced with infertility over the age of 37 but under the age of 43.
When evaluating this study, it is critical to remember that these women had a reasonable ovarian reserve. For women with elevated FSH level or reduced AMH levels, the success would be less. Under those circumstances, moving to IVF immediately offers a patient the information needed to determine if any treatment is effective.