New data contradicts earlier studies on smoking and IVF outcomes.

New data contradicts earlier studies on smoking and IVF outcomes.

Nicotine and Infertility

The success or failure of assisted reproduction can be influenced by many factors, both nonmodifiable (age, ovarian reserve) and modifiable (body weight, lifestyle habits). Smoking belongs to the latter category.

Smoking has important reproductive consequences—early pregnancy loss and adverse obstetric outcome are both more common in smokers—and about 20% of the reproductive-age population smokes.^[1]

The problems, however, start even before conception. Among smokers, infertility is more frequent, and the time to pregnancy is longer. Ovarian reserve is often reduced, and semen parameters tend to be poorer.^[1,2,3]

More specific models are needed to sort out the effect of smoking on key elements (oocytes, sperm, uterine receptivity) of in vitro fertilization (IVF). A recent study^[4] used an oocyte donation model to assess the effect of smoking by egg donors, sperm donors, male partners, and women undergoing IVF.

Smoking-Related Reproductive Outcomes

A retrospective cohort study was based on 4747 donor oocyte recipient cycles. Each donor and recipient were included only once with the outcome of their first treatment cycle. Three categories of daily smoking frequency were compared: none, fewer than 10 cigarettes (light smoking), and more than 10 cigarettes (heavy smoking).

Live birth rates were not significantly different regardless of the smoking status of the donor, recipient, or male partner (Table).

Table. Live Birth Rates by Smoking Status

	No smoking	< 10 cigarettes	> 10 cigarettes
Donors	30.8%	32.2%	32.8%
Recipients	29.8%	31.8%	24.8%
Male Partners	29.4%	30%	31.8%

Using a donor oocyte model, the study found an adverse effect on response to ovarian stimulation, but not on fertilization, implantation, or pregnancy rates.

Why No Tobacco Effect?

Tobacco smoke contains toxins that are harmful to germ cells. Women who smoke enter menopause 1 to 4 years earlier than nonsmokers,^[1] and the effect is more severe among heavy smokers. Men who smoke have lower sperm counts, lower sperm motility, higher DNA fragmentation, and potentially poorer fertilization capacity.^[1,2,3]

Smoking seems to affect implantation as well. Interference with tubal motility increases the risk for ectopic pregnancies. Adverse metabolic and vascular effects reduce the chance of implantation, increase miscarriage risk, and prolong time to pregnancy. Suboptimal spontaneous fertilization could also delay natural reproduction.

The donor oocyte model used in this study allows us to assess individually the effects of smoking on oocytes, sperm, and endometrium. A lower response to stimulation was seen among donors who smoked. Because the gonadotropin dose was similar in nonsmokers and smokers, the lower number of oocytes might be explained by an adverse effect of smoking on ovarian reserve, but markers of ovarian reserve were not reported in this study.

The absolute difference in oocyte yield between smokers and nonsmokers was small. This clinically, but not statistically, significant difference could be related to the very young age of donors. In an older-reproductive-age population, a more marked effect on ovarian reserve could be expected.

Fertilization rates and embryo quality also were not reported in this study, so the effect of smoking on "sperm function" cannot be assessed. Pregnancy and live birth rates, however, were not different, based on the smoking status of male partners. The young age of the donors could be a factor; better-quality, younger oocytes could compensate for aging-related negative effects on sperm.

Endometrial thickness as a surrogate marker for endometrial receptivity was not affected by the smoking status of the recipient. Nor did smoking appear to affect pregnancy loss rates.

Overall, this study did not find a significant detrimental effect of smoking on the outcomes of assisted reproductive technology. Although the donor oocyte model allows us to separately evaluate the effect of smoking on oocytes, sperm, and endometrium, the young age of the donors could explain the outcomes of IVF, which might differ in an older infertile population.

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