Master Class

The Art of Controlling Multiples


Keep in mind that even in small doses, Clomid can have a negative effect on the endometrium. I recommend ultrasonography to check for normal follicular development and to check the lining. If the lining is thin, the implantation rate will be low.

You may decide, after 2 months of Clomid treatment, to try another two to three cycles along with intrauterine insemination. You may also decide that ovulation induction or IVF is more appropriate.

If you are a general ob.gyn. who is performing superovulation induction with hormones, my advice is to judge your comfort level with hormonal stimulation, and to establish and maintain a good relationship with an infertility clinic.

Controlling Multiples

With both ovulation induction/enhancement and IVF, there are ways to control the rate of multiple gestations. Your degree of control is less with ovarian stimulation and intrauterine insemination, but you do have some control and it is important to proceed cautiously. If you see that a patient has more than two or three mature follicles and that her estradiol is elevated above the appropriate level at day 3, it's often best to cancel that cycle. The patient may prefer to proceed knowing the risks, but at least she is being counseled.

The guidelines of the Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine are age based, and are meant to help determine the appropriate number of cleavage-stage embryos to transfer.

According to the guidelines, no more than two good-quality embryos should be transferred in patients under age 35. If the embryos are not necessarily of good quality as judged by morphologic criteria, I believe a third embryo can be considered; but in no case should more than three be transferred.

The guidelines also say that for patients with a favorable prognosis, such as those with good-quality embryos or previous successes with IVF, consideration should be given to transferring only a single embryo. I do believe that if embryos are of excellent quality and the patient is young, and especially if the embryos can be cultured to the blastocyst stage and then transferred, it is worth pushing for a single embryo transfer, which dramatically decreases the risk of multiple births.

For patients aged 35-37, the guidelines are that no more than two good-quality embryos—and no more than three in any other case—should be transferred. Patients who are 38-40 years old should receive no more than three good-quality embryos, and no more than four in any other case.

For patients older than age 40, the guidelines state that no more than five embryos should be transferred. And I would recommend that no more than four be transferred in many cases. All these numbers should be decreased, of course, when embryos are transferred as blastocysts.

European specialists routinely transfer no more than two embryos. They usually transfer embryos at the more advanced blastocyst stage, and because they work in systems of socialized medicine, it doesn't matter whether the patient gets pregnant after just one cycle or more. In the United States, a cycle costs $10,000-$15,000, and patients want to get pregnant the first time.

I encourage my patients who have come for ART consultations to visit the neonatal ICU. The visits give them some perspective on the complications associated with higher-order births. I will often raise the issue of selective fetal reduction—posing it as theoretical—when I see a patient for an IVF consultation. Asking patients how they would feel about this possibility prompts them to think and be prepared for it. It also impresses upon patients that the risk of multiples is real if too many embryos are implanted. Selective fetal reduction is an option, but it has its own complications and risks. We always prefer not to reach that point.

One of the most important things we can do to reduce the rate of multiple gestations is to ensure that we work with an experienced laboratory staffed with excellent embryologists and an excellent director. Certain elements of the visual inspection of embryos are standard and reliably consistent, whereas other elements are more subjective. To some extent, each laboratory director has his or her own way of grading embryos, so our attentiveness to outcomes is critical.

Preimplantation genetic diagnosis (PGD) is typically not performed unless a patient requests it. It is recommended for patients who are older or who have certain chromosomal or genetic abnormalities. It is also recommended in some patients with repeat pregnancy wastage. Single cells can be sent out on day 3 of embryo culture and results can be obtained within 24 hours, in time for embryo transfer at day 5.

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