For many women trying to get pregnant through IVF, the final step can feel uncomfortable. Doctors often prescribe a vaginal gel or suppositories to support a pregnancy in its earliest days. But this routine can cause irritation, discharge, and stress. A new study looks at an oral pill that might offer a simpler path—but it comes with a trade-off.
Frozen embryo transfer (FET) is a common part of in vitro fertilization (IVF). After an embryo is placed in the uterus, the body needs a hormone called progesterone to help the pregnancy stick and grow. This is called luteal phase support (LPS).
Currently, the most common way to get progesterone is through the vagina. This works well, but many women find it messy and uncomfortable. It can also cause local side effects like itching or burning.
An oral pill called dydrogesterone (DYD) could change that. It’s easier to take and may be more comfortable. But until now, we didn’t know if it worked as well as the standard vaginal treatment for frozen embryo transfers.
The standard vs. the new option
For years, micronized vaginal progesterone (MVP) has been the go-to choice for luteal phase support in artificial-cycle frozen embryo transfers. It’s delivered directly where it’s needed and has a strong track record.
But here’s the twist: an oral pill called dydrogesterone is gaining attention. It’s selective, meaning it targets the right receptors in the body without causing as many side effects elsewhere. It’s also much easier to take—just a pill, no gels or applicators.
The big question is: does it work as well?
How the body uses progesterone
Think of progesterone as a key that unlocks the door to pregnancy. The uterus needs this key to accept and hold onto an embryo.
Vaginal progesterone delivers the key directly to the door. Oral dydrogesterone works a bit differently—it’s like sending the key through the mail. It has to travel through the body first, but it’s designed to arrive at the right place and fit the lock perfectly.
The body breaks down oral medications differently than vaginal ones. That’s why researchers wanted to see if the oral pill could match the vaginal gel in helping pregnancies succeed.
A small but important trial
Researchers in Italy ran a pilot study between October 2021 and September 2023. They enrolled 150 women who were scheduled for a frozen embryo transfer using an artificial cycle.
Half the women received vaginal progesterone (MVP), and half received oral dydrogesterone (DYD). Both groups started their medication right after the embryo transfer. The study followed them until a pregnancy test confirmed whether the embryo implanted.
The women in both groups were similar in age, health, and fertility history. This helped ensure a fair comparison.
The study found that the oral pill was less effective than the vaginal gel, but the difference wasn’t statistically significant.
About 31.5% of women taking the oral pill had a successful pregnancy, compared to 45.2% of those using the vaginal gel. That’s a difference of about 13 percentage points.
When researchers analyzed the data including all women who started the study (even those who switched medications), the results were similar: 31.1% for the oral pill vs. 44.7% for the vaginal gel.
The numbers suggest the oral pill might not work as well, but the study wasn’t large enough to prove it. The confidence interval was wide, meaning the true difference could be anywhere from a 38% drop to a 12% increase in success rates.
But there’s a catch
This was a pilot study, meaning it was small and designed to test the idea, not prove it definitively. Only 150 women were involved, and the results didn’t reach statistical significance.
That means we can’t say for sure that vaginal progesterone is better. It also doesn’t mean the oral pill doesn’t work. It just means we need more research.
Where this fits in the bigger picture
This study adds to a growing conversation about making fertility treatments more patient-friendly. Oral medications are easier to take and may improve quality of life during a stressful time.
But effectiveness is still the top priority. If the oral pill is even slightly less effective, that could mean fewer pregnancies. Researchers need to find the right dose and timing to make oral dydrogesterone as good as the vaginal option.
If you’re currently undergoing fertility treatment, this study doesn’t change your options today. Vaginal progesterone is still the standard of care for artificial-cycle frozen embryo transfers.
But this research is promising. It suggests that an oral pill might be a future option for some women. Talk to your doctor about what’s right for you. Don’t switch medications on your own.
This doesn’t mean this treatment is available yet.
This was a single-center trial, meaning all participants came from one clinic in Italy. The results may not apply to women in other countries or with different health backgrounds.
The study was also small. With only 150 women, it’s hard to draw firm conclusions. Larger, multi-center trials are needed to confirm these findings.
Researchers plan to conduct larger studies to test oral dydrogesterone in more diverse groups of women. They’ll also explore different doses and timing schedules to see if they can improve success rates.
If future trials show the oral pill is just as effective as the vaginal gel, it could become a new standard option for luteal phase support. But that will take time—typically several years of testing before any new treatment is approved.
For now, the best approach is to follow your doctor’s advice and stay informed as new research emerges.