Spring’s here! The trees are leafing out, birds are chirping, and cute little lambs are in the pastures. Interestingly, some of those pastures have more lambs than others.

This is a story of how a breed of sheep known for giving birth to more twin lambs relates to women struggling with early infertility.

Sheep Genes and Twin Lambs:

More than two decades ago, researchers made an interesting genetics discovery about a breed of sheep known for having lots of twin and triplet births. These sheep, known as Inverdale sheep, carried a high rate of mutation in a gene on the X chromosome.  This gene, which in humans is known as BMP15, turned out to be really important in the early stages of egg development. For sheep and for humans…

The female Inverdale sheep that carry one copy of the mutation are more likely to give birth to twins or triplets. For farmers, this can be a great way to increase productivity. But…  the Inverdale ewes that carry two copies of the mutation are infertile. So this was a genetic mystery in sheep — and, as it turns out, in humans too.

Researchers discovered that the gene, called BMP15 in humans, is active in oocytes and causes the follicle cell to develop into an egg cell. Mutations in this gene cause less of the active peptide, which allowed for multiple follicles to sometimes develop. This leads to a higher rate of twins. But the sheep with double mutations tended to be infertile.(study)

The Inverdale gene isn’t the only mutation that causes both increased fertility — or infertility. Geneticists have discovered multiple mutations in sheep breeds around the world in two genes (BMP15 and GDF9) that work together at that critical juncture when the egg cell begins to develop.

Premature Ovarian Insufficiency (POI):

This isn’t just a story about sheep!

The same genes affect the development of human egg cells also. Women who carry mutations in these genes can be at an increased risk for premature ovarian insufficiency. The mutations are also linked to increased odds of having fraternal twins.

What is POI?

Premature ovarian insufficiency, also called premature ovarian failure, is the term used when the ovaries stop working normally before age 40. This can mean irregular menstrual periods, irritability, hot flashes, and problems getting pregnant. (article)(article)

This article talks about the 2 most common tests to determine ovarian reserve.

For the majority of women with POI, doctors will say that the cause is ‘unknown’.

On the contrary, here are some of the known causes of POI:

• Genetics
• Certain autoimmune diseases
• Exposure to chemotherapy
• Cigarette smoke

Understanding ovulation and follicles:

For ovulation to occur each month, an oocyte goes through a development process to turn into an egg cell that is ready for fertilization.  It is a complex process that occurs in several stages.  This is why the myth that egg quality cannot be improved is false (even if your doctor says it).  This maturation process is not predetermined at birth but rather happens as an adult and is influenced by your lifestyle so can be optimized, even into your 40s.

The oocyte is contained in a follicle that secretes hormones needed for the egg cell maturation.  For the follicle to mature, signaling molecules and certain hormones need to be at the right levels at the right time.

The protein called bone morphogenetic protein 15 (BMP15) regulates the reproductive hormones during the first stages of the follicle developing. BMP15 combines with another growth factor protein called GDF9. Researchers have recently shown that BMP15 and GDF9 regulate the transition of the follicle into the second stage of development. (study)(study)

Several studies of women with POI show that it can be caused by mutations in GDF9 and BMP15. Interestingly, some of the exact same mutations that increase the probability of fraternal twins are also detected in women with POI. (study)(study)

These follicle regulating genes, though, are just one of the causes of POI.  There are other mutations in hormone receptors that are also implicated in the risk for POI and there are other environmental causes.

Genetic variants associated with POI:

If you have genetic data from  23andMe or AncestryDNA, you can check your raw data to see if you carry some of the BMP15 variants.

While these variants increase the risk of POI, having the variant doesn’t mean that you will absolutely have POI. It is a statistical increase in the risk. There could be other genes and environmental factors involved.

Check your genetic data for rs3810682 (C9G):

• GG: increased risk of POI, altered hormone levels (study)(study)
• CG: increased risk of POI
• CC: normal

Check your genetic data for rs17003221 (852C>T):

• TT: altered hormone levels, associated with ovarian insufficiency (study)(study)(study)
• CT: increased risk of POI
• CC: normal

POI or early menopause is known to have a hereditary component — it ‘runs in families’. And the same genes that are involved in POI are also tied to increased risk of having fraternal twins. It would make sense, then, that those fraternal twins would be likely to inherit the genetic variants that can lead to POI. In fact, a study of twins in 2007 found that twins are at a 3 to 5 fold increase in risk for premature ovarian failure .(study)

What can you do if you have POI due to a genetic variant or other cause?

The first step for women with POI is to talk with their OB/GYN and find out about the conventional medical options for fertility. There are hormone treatments that may be appropriate or other interventions that your doctor may suggest..

But most women are left without many answers when dealing with POI. This can be frustrating and heartbreaking.

While genetics can stack the deck towards having POI, it is often the case that there are multiple causes involved. Addressing these causes may give you the edge that you need to get pregnant.

Environmental toxins:
Several environmental factors have been implicated in the risk for premature ovarian insufficiency. Numerous studies show that women dealing with POI have higher levels of certain toxins such as phthalates, BPA, and pesticides in their blood.

Avoiding exposure to toxins, eating organic when possible, and avoiding cigarette smoke are all important when dealing with POI. (study)(study)

The Right Diet:
Providing your ovaries with a surplus of nutrients can provide an optimal environment to overcome genetic tendencies so the eggs can thrive.  Nutrients such as filtered water, healthy saturated fats, proteins, antioxidants, and trace minerals are all necessary for a healthy baby yet often deficient in the modern diet. Knowing if and when you ovulate:
Women with POI often deal with irregular periods, making it hard to know the timing of ovulation.  Working with an acupuncturist or other natural health care practitioner may regulate your periods.