In Medline Academics’ Embryology Training our learning objectives are to define infertility and the commonly used terms in the field, identify causes of male and female infertility, understand basic infertility evaluation, understand infertility treatment, we’ll also discuss about what the term assisted reproductive technology (ART) means, and lastly, we’ll discuss about the various expansions of IVF / ART that are becoming increasingly relevant. Medline Academics offers hybrid program for practicing clinicians to upskill themselves in the field with the most recent developments in the field. This rare opportunity to ‘earn and learn’ is rather rare in this field and with our institution giving this opportunity, 500+ students have successfully carried forward the legacy of Padma Shri Prof. Dr. Kamini A Rao and the excellence of 4 decades forward.
Infertility
First, we need to define the concept of infertility. Although the male can be the reason behind a couple’s infertility, the diagnosis of infertility is most contingent on the female, because that’s what’s most difficult to treat. For women less than 35, infertility is the failure to conceive after 12 months of regular unprotected intercourse, obviously without the use of contraception. For women older than 35, infertility is the failure to conceive after 6 months of regular unprotected intercourse.
Fecundability
The next term is fecundability. Fecundability is the probability of achieving a pregnancy in one single menstrual cycle. That is all based on regular cycles every 28 to 35 days. For the average couple, fecundability is about 22%. Not to be confused with fecundability is fecundity, which is the probability of having a live birth within one cycle, or rather, having a live birth because of one cycle. Obviously, this is going to be less than fecundability, because it needs to incorporate the possibility of miscarriage each cycle. For the average couple, fecundity is about 15 to 18%. And just to give everyone a good idea of what is normal and what is abnormal, 85 to 90% of couples conceive within 12 months of intercourse. That means 10 to 15% of the population is infertile, and that represents the commonly cited statistic that infertility affects approximately 1 in 6 couples.
Causes of infertility
- Of all infertility workups, about 35% of cases are attributable to male problems. That includes pre-testicular, testicular, and post-testicular.
- About 35% of cases stem from problems with the female partner.
- It’s thought that 20% of infertility may be caused by things that affect both genders equally, like drugs, environmental exposures, and the deleterious effects of insufficient or excessive diet and exercise.
- And lastly, about 10% of infertile couples are ultimately diagnosed with unexplained infertility when all causes have been ruled out.
- It is a diagnosis of exclusion. These are some of the possible diagnoses in the spectrum of male infertility. Pre-testicular causes usually refer to problems proximal to the gonads. This usually means problems with the hypothalamus, pituitary, and gonadal axis. Testicular causes can be loosely divided into genetic and non-genetic problems, like Klinefelter’s, for example, which is the most common genetic cause of testicular infertility. Non-genetic causes include things like drugs, infections, trauma, and varicoceles.
- Post-testicular causes are things that don’t allow normal transport of sperm through the ductal system. These can be congenital or acquired. Men who are exposed to DES in utero, for example, can have hypospadias, cryptorchidism, or other blockages. Congenital absence of the vas deferens is sometimes seen with cystic fibrosis patients. Non-genetic causes are things like infections, surgery, and trauma as above. Female causes are a little easier to visualize, in my opinion.
- They are called factors. First, there is cervical factor. This is usually as a result of stenosis that prevents sperm from reaching the egg in the fallopian tube.
For those of you who are women in the audience, you actually had most number of eggs, about 7 million when you were a foetus, about 28 to 30 weeks inside your mother’s uterus. By the time you were born, you’ve actually lost most of them and are down to 2 million eggs. When you have your first period, you’re down to about 500,000.
If you don’t use birth control or ovarian stimulation, you’ll ovulate about 400 to 500 of these eggs in one entire lifetime. There are tests that you can use to check ovarian reserve, like FSH and AMH, but no single test is a perfect test. In order to determine the true ovarian reserve, you have to use the entire clinical picture, which is also beyond the scope of the clinical embryology courses in Bangalore.
Another cause of ovarian factor is anovulation. This happens more often than you know, and when you hear of women having periods only 3 to 6 times a year, that’s probably what’s happening. This is most commonly caused in the USA by obesity, but can also result from other interruptions in the HPO or hypothalamus pituitary ovarian axis.
Tubal factor is pretty straightforward. If a patient has a previous sexually transmitted disease, tubal surgery or ligation or other injury, the tube is sometimes the reason why the egg and sperm can’t interact. Very rarely, there are some reports that fallopian tubes can actually twist and you get a fallopian tube torsion, which then results in a necrotic and non-viable tube.
Lastly, there is a broad category of peritoneal factors. This can be anything from pelvic inflammatory disease to adhesions to endometriosis. Endometriosis is its own lecture, but it is when endometrial tissue is actually found outside of the uterus.
It’s a pro-inflammatory state that is toxic to eggs and embryos, so it’s not good for pregnancy, obviously. Sometimes it moves to strange places like the brain, the eyes, and the lungs. Interestingly enough, when it’s in the lungs, people sometimes say they have monthly bloody coughs when they have their periods.
Causes that affects male and females non-specifically
In the environment, things like radiation, lead, heavy metals, pesticides can all interfere with gonadal function. Drugs like tobacco, alcohol, marijuana can also interfere with sperm function and ovulation.
Diet and exercise can also cause problems with the axis. When females exercise too much, they can have something called hypothalamic hypogonadism, which is where the entire axis slows down, and they have amenorrhea and anovulation. In males, this may actually happen too, but it’s not as clear.
What may be the male manifestation of exercise is actually oligospermia, or decreased sperm count. Obesity can actually cause the same thing as well. So on to the assessment.
The first part of a good evaluation is a good history and physical. You need to pay specific attention in the OBGYN history to things like, has the patient gotten pregnant before, what has changed in her life between pregnancies, things like weight, surgery, or her partner.
Also, you need to know about menstrual history and ask about what the patient’s bleeding pattern is. Is the patient heavy? Maybe she has fibroids or polyps. Perhaps she’s not bleeding at all, or maybe she’s anovulatory. If she has a lot of pain before each cycle, it may suggest endometriosis.
For the male, the questions are often not as revealing, but you should ask about any traumas, surgeries, and medications, and whether or not patients have fathered children before this. But keep in mind that studies actually say that 2-4% of patients actually have mistaken paternity.
So, fathers are actually not who they think they are, and some papers actually advocate that as much as 5-10% of the world’s population don’t have the right father. The physical exam is also important and can be helpful when you find something obvious like exophthalmos. Chromosomal problems can oftentimes be undetectable, but these things can tip people off if they have syndromic findings of episcopal fades, low-set ears, webbed necks, etc.
Looking for an Infertility Specialist in Bangalore? Dr. Kamini Rao Hospitals offers thyroid examination that can also be helpful in such cases. A GYN exam is important to look for stenosis or evidence of hyperandrogenism, fibroids, ovarian masses, or anything else abnormal. When a provider is testing for a cause of infertility, there are specific tests you can check to check a specific anatomical or biochemical practice. Located in Kumarapark, this centre offers treatment as well as trains future infertility specialists.
In practice, however, sometimes clinics will actually order all the tests at once in order to get answers as quickly as possible. Sometimes you only need to order specific tests based on the history. Without going into details, we’ll just talk about how to evaluate each of the factors on this slide. Link
To test the uterus, a hysterosalpingogram, or HSG, can be helpful. An HSG is when you inject radio-opaque dye into the cervix and take a real-time X-ray to look at how the uterine cavity traces out. It’s also useful to see if contrast spills out of the tubes because then you can evaluate for tubal patency.
Ultrasounds are also commonly used to evaluate GYN organs. It may be counterintuitive, but a pelvic ultrasound is actually better than any other imaging test to visualize these organs. A related test is actually saline infusion sonography, or SIS, where you fill up the endometrial cavity with saline to see if polyps or submucous fibroids are showing up more clearly.
If you see something, you can then do a hysteroscopy, where you actually go to the operating room to put a camera in the cervix, look inside the uterus, and use instruments to cut or burn polyps away. MRIs or CT scans can sometimes be more helpful, but usually people only need ultrasounds. To evaluate ovarian factor, you need to do things like basal body temperature to see if a woman is ovulating each month.
You can also check things like an FSH and estradiol level, as well as the AMH or anti mullerian hormone to see how much ovarian reserve is left. Antral follicle count is an ultrasound-guided follicle count just to see how many follicles grow early each month, and it can also be a major determining factor in ovarian reserve. Tubal factors can also be tested using an HSG, as stated above, or with laparoscopy. With laparoscopy, it’s actually a surgery where you look at the tubes and visualize any damage or abnormalities that was inconclusive on imaging. Also, you can push dye through the cervix, and if you see dye spill out during the laparoscopy, that is called a successful chromo perturbation. For the male partner, there’s actually a whole host of problems that can happen, but everything starts with one test, which is a semen analysis.
Instead of going into male factor specifics, this is just an overview and review of terms that is used to describe semen. Azoospermia is no sperm, oligospermia is few sperm, astenozoospermia is motility less than 50%, teratospermia is abnormal morphology, hypospermia and hyperspermia are pretty self-explanatory. Treating infertility, if you think about it, is pretty logical.
If you have identified the limiting factor, you just need to bypass that particular factor that’s preventing conception. For cervical stenosis, you can treat that with antibiotics, if appropriate, or use intrauterine insemination, or IUI, where you push washed semen into the uterus around the time of ovulation. Treating uterine factor depends on how bad the condition is. If it’s something serious, like congenital absence of the uterus, then that patient will need to talk about surrogacy using a gestational carrier’s uterus.
Ovarian factor is treated with medications that encourage a stronger ovulation response. You can do this with any number of medications like clomiphene, aromatase inhibitors, gonadotropins. Tubal and peritoneal factors can be treated surgically or actually by in vitro fertilization. If the tubes are tied and the leftover stumps are long enough, you can actually reconnect the tubes to allow for future pregnancies. This may unfortunately lead to more ectopic pregnancies. If there are something like hydrosalpines, those things are actually toxic to the egg, so resecting those prior to having IVF cycle actually decreases the inflammatory response.