Deborah Howell (Host): This is The Time To Talk Fertility podcast. I'm your host, Deborah Howell. Understanding the causes of infertility can be overwhelming, but knowledge is power. Today, Dr. Megan Sax, a Reproductive Endocrinologist here at FCI, joins The Time To Talk Fertility podcast to break down the most common reasons behind infertility; from PCOS and endometriosis to hormonal imbalances, fibroids, and even lesser known factors that might be affecting your fertility.

She'll also shed light on how infertility is diagnosed, the early warning signs to watch for, and the latest treatment options for both men and women. Dr. Sax, nice to have you back with us.

Megan Sax, MD: Hi, Deborah. It's great to be back. Thanks for talking with me.

Host: Absolutely. And let's go ahead and begin with the big picture. Can you provide an overview of the most common causes of infertility?

Megan Sax, MD: When a patient visits with me to discuss fertility, I always start by reviewing what we need to make a healthy pregnancy; communication from the brain to the ovary to grow and release an egg or ovulate, adequate semen parameters, open fallopian tube so that the egg and sperm can meet and a healthy uterus for the pregnancy to grow. A deficiency in any of these can result in infertility. To make a complicated topic a little easier to grasp, I usually like to think of this as divided into thirds, a third due to a male factor, third due to a female factor, and the remaining third being due to combined or unexplained factor. In the female factor category, about 40% is usually due to ovulatory dysfunction. Below egg reserve due to advanced age and anatomical issues involving the uterus or fallopian tubes can also be commonly encountered.

Host: Okay. And how do you go ahead and diagnose infertility in patients?

Megan Sax, MD: So the diagnosis of infertility depends on the female patient's age. For women under 35-years-of-age, infertility is diagnosed after 12 months of trying to conceive, but after only six months of trying to conceive at age 35 and older. Now, despite actual diagnostic criteria for infertility, it's important to note that an infertility evaluation may be indicated sooner than six to 12 months, if there's other concerns like irregular or very painful menstrual cycles. Additionally in women older than 40, a more immediate evaluation may be warranted as we see decreased rates of pregnancy and increased risk of miscarriage with increasing age.

Host: Got it. Now, are there any early signs of fertility issues?

Megan Sax, MD: Sure. Early signs may include irregular or very painful periods, which can be suggestive of polycystic ovarian syndrome or endometriosis, respectively. If menses isn't occurring every 21 to 35 days and you're trying to conceive; then it's time to see a women's health provider or fertility specialist. And I should mention that when I say 21 to 35 days; this is counting day one as the first day of full flow bleeding up until the next first day of full flow bleeding in a subsequent cycle.

For men, erectile or sexual dysfunction may be associated with abnormal semen parameters, but more frequently men will not exhibit any early signs of fertility issues.

Host: Okay. You mentioned a couple of conditions. How do conditions like polycystic ovary syndrome or PCOS and endometriosis affect a woman's fertility? 

Megan Sax, MD: PCOS and endometriosis are both incredibly common and we see them very frequently in the fertility clinic. PCOS may affect up to 13% of reproductive age women. While endometriosis is estimated to occur in six to 10%. Among infertile women, these numbers are even higher.

For example, endometriosis is prevalent in up to 38% of women facing infertility. There's also a very strong genetic predisposition to both of these disorders with a seven to tenfold increased risk of endometriosis in patients who have a first degree relative who's affected. In short, both disorders may cause issues with ovulation leading to infertility, but in PCOS, the eggs are usually there. We just need adequate hormonal stimulation for the eggs to be recruited, develop, and ovulate.

In endometriosis, we may have additional issues. And in this disorder we see the endometrium or the lining of the uterus growing outside of the uterus, and it can cause scar tissue and distort anatomy, like the fallopian tubes. It can also deplete eggs and even negatively affect egg quality. 

This may be through a number of mechanisms, but is most likely due to the creation of an inflammatory environment, negative effects on local hormone production if a cyst or endometrioma disrupts the ability of the ovary to produce a normal hormonal balance, or it could be due from reduced blood flow to the ovaries.

Host: Now, can you tell us what are the success rates of fertility treatments for endometriosis and PCOS and do they differ from other infertility patients?

Megan Sax, MD: This is a great question, and if you were to do a literature review on either disorder, you'll find statistics on success ranging all over the place depending on severity of disease and type of fertility treatment. No matter the diagnosis, once I've completed a fertility workup with a patient, I provide them with estimates of percent success for different treatment options, and then we make a decision together on how to proceed.

Chance of success will usually vary most greatly based on age, anatomy, semen parameters, an ovarian reserve, which is determined by Anti-Müllerian hormone, which we detect in the blood, as well as how the ovaries appear on ultrasound. Nonetheless, I would say PCOS patients often have a relatively high success rate as their ovarian reserve is typically quite good. The ovaries just may require additional stimulation.

Similarly, if a patient with endometriosis does not have significant ovarian involvement and they are overcoming blocked fallopian tubes, for instance, being their only problem, I would expect their prognosis to be very good as well. So overall, success rate is going to depend on the severity of either disease and can be very subjective.

Host: Okay. Got it. Now let's talk about something so many women suffer from. We're talking about fibroids. What are they and how do they affect a woman's fertility?

Megan Sax, MD: Deborah, you are so right. Uterine fibroids are so common that we actually find them in up to 70% of women in their lifetime. So uterine fibroids are benign tumors that can grow and cause irregular bleeding, bulk symptoms or infertility depending on their size and location. Although fibroids are not usually the sole cause of fertility, it's important to determine whether a fibroid may be affecting the inner part of the uterus where a pregnancy grows, or distorting the anatomy and preventing a pregnancy from occurring. We can test for this by doing an ultrasound and putting a little saline in the uterine cavity, which is called a saline infusion sonogram.

Host: And another thing I've been wondering about, how does age affect fertility? 

Megan Sax, MD: So female age is one of the hardest factors to overcome when it comes to fertility treatment. A woman is born with all the eggs they will ever have, so as we age our eggs age alongside with us. This can result in having decreased ovarian reserve as well as an abnormal amount of genetic material or chromosomes in the eggs and increases the risk of miscarriage.

In other words, pregnancy rates decrease and miscarriage rates increase as we age. We see this trend is even more obvious after age 35, increasing more drastically with each passing year. In fact, the Society for Reproductive Technology reports the chance of live birth from IVF in women under 35 to range from 30 to 50%, but this decreases to five to 20% in women over 40.

In contrast in patients with advanced age who use eggs obtained from healthy young donors, 51% of embryo transfers will result in live birth regardless of the age of the woman carrying the pregnancy. So it's really the age of the egg that holds so much power here.

Host: That's so fascinating. So we've been talking about the basics, but what are some lesser known causes of infertility that people might not be aware of?

Megan Sax, MD: I would say other hormonal causes like abnormal thyroid hormone levels, or elevated prolactin hormone, or the hormone associated with breast milk production. Additionally, some autoimmune disorders have been found to be related to infertility, but we usually only screen for autoimmune disorders if there's a particular concern or a strong family history.

Host: Okay, and what tests are available to assess sperm health?

Megan Sax, MD: The recommended test would be the semen analysis where we look closely at the sperm concentration, motility, and morphology. There are additional evaluations that may be offered if we detect a severe abnormality, but usually a semen analysis will suffice to help gauge what treatments can be offered and what will be effective on the male side of things.

Host: And are there medical treatments or interventions that are available for a male factor infertility?

Megan Sax, MD: Depending on how severely abnormal the semen analysis parameters are, we may be able to overcome male factor infertility with inseminations, where we place the sperm in the uterus with a catheter or in vitro fertilization where the eggs are taken out of the body under anesthesia and combined with sperm to create embryos.

Mild derangement may improve with the addition of supplements, but in some circumstances, certain procedures like sperm aspiration or extraction may need to be performed in order to obtain sperm for testing and treatment.

Host: Okay. I think you're going to like this question. What treatment options are there for those struggling with infertility?

Megan Sax, MD: Treatments can really range from timed intercourse, to inseminations, to in vitro fertilization, depending on what is suspected to be the cause of infertility and the reproductive goals of the patient. In some circumstances, it may be recommended to proceed with donor sperm, eggs or embryos. So there's a lot of options out there.

Host: That's great news. Final question for you, Dr. Sax. How do you determine the most appropriate treatment plan for a patient based on their specific fertility diagnosis and what factors influence your decision making process?

Megan Sax, MD: We are so fortunate in this day and age to have a significant amount of research to refer to in order to make treatment plans that will yield the greatest chance of having a live birth based on a patient's diagnosis and age. I always discuss with my patients what their ideal number of children would be and give estimates for success.

I want to make sure that by the end of our conversation, they feel confident with the plan we've developed together.

Host: Is there anything you'd like to add to our conversation?

Megan Sax, MD: Oh, I would love for patients to know, please don't apologize for asking questions. We know this is tough stuff to understand and that the stakes of fertility treatment are high. There's emotions, time, costs. A huge part of being a fertility doctor is being a teacher and empowering those facing fertility challenges with knowledge. So bring on all the questions. We're here for you.

Host: Couldn't agree more. It's been so wonderful having you again, Dr. Sax. Thanks so much for being with us today to share your expertise.

Megan Sax, MD: Thank you for the great discussion. I hope this will help patients to kickstart their fertility journey and hit the ground running.

Host: I'm sure it will. That was Dr. Megan Sax, a Reproductive Endocrinologist here at FCI. Visit fcionline.com for more information. Or call 877-324-4483 to book an appointment with a fertility specialist. If you enjoyed this podcast, you can find more like it in our podcast library and be sure to give us a like and a follow if you do.

This has been The Time To Talk Fertility podcast. I'm your host, Deborah Howell. Have yourself a terrific day.