Fertility FILE

Fertility FILE 101: ENDOMETRIOSIS

Endometriosis is an a condition where the tissue that normally is found inside the uterine ends up growing and proliferating outside the uterus. It affects an estimated 1 out of 10 women in the world. However, that estimate is subject to dispute because the only sure way to tell if someone has endometriosis is to look surgically.

Every month, in a normally cycling woman, the lining of the uterus builds up in preparation of nourishing any fertilized egg (embryo) that comes into the uterus. If no viable embryo shows up, then the lining is shed in a process known as menstruation. Most of the blood and tissue will flow out the cervix and out of the body. However, in every woman who has open tubes, some of the blood and tissue will flow backwards through the tubes and into the abdominal cavity.

Under normal circumstances, the body's immune system will clean up this material. However, in an abnormal circumstance, the internal buildup of menstrual debris overwhelms the body's clean-up capacity and results in the tissue building up, taking hold and digging in. These endometriosis implants can cause intense pain (but not always) and they can contribute to infertility. Some of the ways that endometriosis can cause infertility is by scarring the tubes and scarring the areas outside the tubes. The process also creates a hostile inflammatory environment so that eggs die faster, even if they somehow traverse the obstacle course created by the scarring and make it into the tubes.

Solutions to address the pain include surgery and medications. Solutions to address the infertility include IVF (to completely bypass the endometriosis) or a combination of fertility drugs and insemination. The principle behind using fertility drugs and insemination is related to flooding the system with excess eggs and sperm. Even though the eggs are still subject to a hostile tangled environment there is an advantage to having multiple eggs. There develops a higher chance that even though most eggs will be trapped and die, perhaps a single lucky one can elude the endometriosis and make it to safety to be fertilized and form a baby.

Fertility FILE 101: MISCARRIAGE

There are extreme highs and lows in the typical work week of a Reproductive Endocrinologist. Throughout my career, in one manner or another, I’ve had the chance to share in the joys of families as they have welcomed over eight hundred happy healthy babies into their lives. I’m ever thankful for these experiences. However, along with those “good” pregnancies, there have been hundreds of other times when I’ve endured alongside my patients their utter sorrow as they suffer a pregnancy loss. Many of you may yourselves have had one or more miscarriages before. And only you can understand the many thoughts that run through your minds during these tragic events.

So many questions come to your mind. Was it something I ate? Was it that argument I had at work with that difficult client? Should I not have lifted that bag of groceries? It’s normal human nature to search for a reason or cause for events. However, in the case of an isolated first miscarriage, there is usually no reason other than for the cruel truth that miscarriages “just happen”. Even the healthiest women will suffer miscarriages. The rate in the general population is about 1 out of 6 pregnancies ending in a loss. For women over 35, that risk is even higher. This is usually due to the fact that sperm and eggs are not always perfect. If the specific sperm or egg that happened to create this pregnancy was in any way imperfect, it could be just good enough to conceive, but not good enough to thrive and survive. Nothing in the world could have prevented it. Yes, there are other miscarriages that arise from maternal factors. In these cases, a genetically perfect conception fails to survive because of a bad environment inside the uterus. This might be due to a physical defect, such as a fibroid or polyp or it might be due to a hormonal abnormality.

After sufficient grieving, the most important thing to do is to make the right decision. For most people, the right decision is to just go back to trying on your own again. For others, the right decision is to go seek help.

Many factors influence what is the right decision:

AGE: If you are younger, then it is not as crucial that you get a thorough workup and are you usually told to wait and get checked only if it happens again. OB/Gyn textbooks classically use three miscarriages as the threshold at which you should launch an investigation. However, if you are over 35, you might want to seriously look into it even if you’ve had two miscarriages. The reasoning is because if there is something treatable, then you need to take action before you run out of precious time in your lifetime of fertility.

NUMBER OF MISCARRIAGES: If this is your first miscarriage, most doctors would not recommend a workup. If this is your third or greater miscarriage, then most doctors would agree that a full workup is in order.

NUMBER OF HEALTHY PREGNANCIES: Someone who has six healthy children with three miscarriages interspersed between those healthy pregnancies is not in as great a need of a thorough workup as someone who only has three miscarriages and no other pregnancies.

SUSPICION OF A SPECIFIC PROBLEM: Women who have other clues for health problems, such as abnormal bleeding, known uterine problems, chronic medical issues or a significant family history of genetic or medical problems should consider getting help sooner rather than later.

FERTILITY: A woman who gets pregnant once every two years and has three miscarriages over six years has greater urgency to seek help than one who had three miscarriages in one year and seems to get pregnant quite easily.

KEY POINTS TO CONSIDER:
- Isolated miscarriages, while very sad, are part of normal human reproduction. The focus should be on getting as healthy as reasonably possible (diet, exercise, weight control, avoidance of smoking and other bad habits, stress management) and getting emotionally ready to conceive again.
- After a miscarriage, avoid searching for ways to blame yourself or looking for some real or imagined reason that caused it.
- If time is not urgent for you, then wait two to three months to emotionally recover. Spend that time catching up with the things in life that got put on hold during the weeks of dealing with the miscarriage. Take a break and enjoy activities that you may have put off for a time. However, if time IS urgent for you (if you are older, for example), then it’s probably better to just keep trying right away rather than wait three months. Don’t necessarily seek medical assistance, but don’t use contraceptive measures to avoid getting pregnant.
- Contrary to popular belief, for the majority of women who have had miscarriages, odds greatly favor that the NEXT pregnancy will be a healthy one rather than another miscarriage.
- Recurrent miscarriages should be seriously addressed as there might be a treatable cause.

Watch for future posts that discuss some of the causes of habitual miscarriage.

Fertility FILE 101: REPRODUCTIVE ENDOCRINOLOGIST

A Reproductive Endocrinologist (RE) is a doctor (M.D. or D.O.) who has completed specialized training in the field of medicine dealing with the hormones that govern conception. Sometimes, rather than calling them RE's, people refer to them as infertility specialists.

However, the term infertility specialist is a generic, unofficial term and can really apply to anybody who has a particular interest in fertility. Any family medicine doctor, general OB/Gyn doctor, acupuncturist, herbalist, nutritionist or other type of medical personnel can label themselves as a specialist in infertility.

In contrast, to consider oneself a reproductive endocrinologist, one must go through a very specific educational track. They must first graduate from college and attend four years of medical school. They then must get accepted into a residency in OB/Gyn where they will spend four years learning how to deliver babies, operate on the uterus and ovaries and take care of all aspects of women's health. During this time they will pass written examinations and then officially get their license to practice medicine. After these four years, they must apply to the limited number of accredited RE programs in the US. Once accepted, they will spend an additional three years focusing on learning infertility diagnosis and treatment.

The typical work week consists of meeting with patients to discuss their fertility issues, performing office procedures such as ultrasounds and inseminations, performing surgery such as laparoscopy and hysteroscopy and performing ART procedures such as egg retrievals and embryo transfers, all for the purpose of helping couples have babies.

While there is no clear shortage of RE's, the demand for their services is great and continues to increase as society displays a trend to delay childbearing until older age when it becomes more difficult. It is estimated that there are 1 million practicing physicians in the US. Out of those, there are about 1400 RE's or 1 out of every 700 doctors, making for a very limited subspecialty.

Fertility FILE 101: It's Just HORMONES Again

I polled some non-medical friends and acquaintances on what came to their minds when they heard the word HORMONE. The responses varied greatly from raging emotions to vivid sexual imagery. Suffice it to say that this word is one for which the difference from its everyday general usage to its intended scientific meaning is huge. In medical terminology, a HORMONE is very simply a chemical substance which acts a biological messenger.

The reason we associate it with emotions and drives is because one of the targets that hormones act on is the brain, which of course, governs our feelings and actions. When it comes to fertility, hormones play a key role. The brain has to talk to the ovaries to tell them prepare an egg for ovulation. The ovaries have to tell the brain that they are responding. They also have to tell the uterus when to get ready for possible implantation of an embryo. If a pregnancy is successfully established, the new set of hormones produced by the developing fetus tell the body that a pregnancy has occurred. This can lead to nausea, moodiness, cravings, breast changes and the many other symptoms associated with pregnancy.

Here are some of the key hormones involved in reproduction along with the basics regarding each one.

FOLLICLE STIMULATING HORMONE (FSH): This hormone comes from the brain (more specifically the pituitary gland, which hangs from the base of the brain). It travels through the bloodstream and tells the ovaries to get an egg ready. Once the egg begins to respond, another hormone (estrogen) is sent back to message the pituitary to ease up on the FSH production. This is called feedback. Women whose eggs are all too old or too few in number will fail to respond to the FSH. When this happens, the pituitary does not ease up, but rather starts cranking out ever higher levels of FSH. This is why high levels of FSH are a sign of ovarian failure or near-failure.

A very different type of problem happens in women who are anorexic, very stressed, or extremely thin. They may not produce FSH properly and therefore, may not develop their eggs properly. This could result in them not having periods.

Women with PCOS produce FSH normally. But their ovaries are surrounded by high levels of male hormones and therefore need even higher levels of FSH in order to properly develop the eggs. One way to get this accomplished is to boost your own natural FSH production using drugs like Clomid. Another way is just to supply large amounts of FSH from outside sources, rather than counting on you to produce it yourself.

ESTROGEN: This hormone is produced by the developing eggs. It is what makes the cervical mucus more watery. It is what makes the uterine lining thick and healthy and ready to support implantation. Estrogen goes back to the pituitary and shuts off the FSH.

LUTEINIZING HORMONE (LH): This comes from the same place as FSH. While FSH tells the eggs to develop, LH signals the eggs to release. Once the LH signal is sent to the ovary, the egg releases in about 36-40 hours later. This is the magic hormone that is measured in the ovulation prediction kits.

PROGESTERONE:  After ovulation, this is made in large quantities by the remaining “shell” of the follicle. It is responsible for the rise in basal body temperature seen after ovulation. If the progesterone levels drop, the lining will come out as a period.

HUMAN CHORIONIC GONADOTROPIN: This hormone is made by the fetal tissue and is what makes a pregnancy test turn positive. This hCG also happens to be available as a drug to trigger ovulation because it mimics the action of LH.

Watch for more details about each of these hormones in future posts. As you can see, there is actually nothing sexy or emotional about hormones themselves. However, by regulating our reproductive systems, they actually do play a crucial role in the wonderful feeling we get from watching the babies that result.

Fertility FILE 101: POLYCYSTIC OVARY SYNDROME

Polycystic Ovary Syndrome is a condition that affects close to 10% of the women in the world.

Women who suffer from this condition usually have many of the following findings:
Infertility - PCOS patients are sometimes able to get pregnant naturally, but many of them will have difficulty.
Obesity - PCOS patients generally have greater body mass than women without PCOS. However, it is  not univeral. A few PCOS patients have normal or even extra lean body mass. Another general finding is that PCOS patients tend to gain their excess weight around the midsection (as opposed to the thighs or hips).
Excess Male Hormones - Women have low levels of male hormones, but women with PCOS have higher levels, leading to the possibility of facial hair, chest hair, acne, male-pattern hair thinning, oily skin and bloating.
Irregular or Inconsistent Menses - PCOS patients often do not ovulate every month. Some of them can go a whole year without a single ovulation or period.
High Risk of Cardiovascular Disease - Women with PCOS are generally more prone to high blood pressure, high cholesterol, heart attacks, strokes and diabetes.

While there is no cure for PCOS, there are many available helpful interventions that can address the issues of infertility, irregular menses, obesity, excess male hormones and health risks.

In future posts, we'll look at the specific interventions that can help improve the quality of life for women suffering from PCOS.

Fertility FILE 101: OVULATION

Ovulation is the rupturing of a follicle with subsequent release of an egg.

Women are born with 1-2 million eggs. These lay dormant in the ovaries wrapped in a layer of cells. A FOLLICLE is the name given to an egg surrounded by the layer of cells (known as granulosa cells).

Each month, out of the entire supply of follicles, a small group of them (known as the recruited cohort) begin to grow. Most of the time, under natural conditions, only one of the follicles grows to the mature state. This is called the dominant follicle. The rest of the follicles that month only grow partially and are wasted, lost forever. Under conditions when a woman takes fertility drugs, many more of the original group of follicles can be rescued so that they, too, have a chance to initiate a pregnancy.

From many lectures to my medical students, one analogy that seems to help clarify is to envision the follicle as a slowly-growing "water balloon" which has a tiny grain of sand inside (this sand represents the egg). When the follicle reaches about 18-20mm in diameter and a special hormonal signal, called the LH surge, is sent to it, it will undergo biochemical changes that eventually result in the popping of the follicle and the release of the egg. This special hormonal signal is what those urinary ovulation kits are designed to detect.

Fertility FILE 101: SEMEN ANALYSIS

A semen analysis is a test to evaluate the husband's sperm.  It is one of the least expensive, least invasive tests in the standard fertility evaluation. To perform the test, the husband is asked to abstain for at least two days, preferably three, and no more than seven days. He is then instructed to ejaculate into a sterile cup and bring the sample to the office within one hour.

Upon receipt of the sample, the first thing done in the laboratory is to look at it and describe anything unusual about its color or appearance. Next, the sample is measured for its volume. Finally, a drop of it is placed into a special counting chamber, such as the Makler chamber, which is what we use in our office.

By counting how many sperm fall into the squares of a precisely calibrated grid and by distinguishing the moving sperm from the non-moving sperm, a sperm count and motility are calculated.

The basic two features evaluated are the sperm count and the sperm motility. The count refers to how many sperm there and the motility refers to how many of them are moving.

There are also more detailed features that can be determined about the sperm, such as the morphology and the DNA integrity.

Fertility FILE 101: The UTERUS

The uterus is the female organ which serves as the baby's home during a pregnancy. It begins as a muscular organ about the size of an orange and slowly grows during pregnancy to be large enough to accommodate a full term baby. 

The lowest part of the uterus is the door by which the baby eventually exits. This is know as the cervix. There are also two openings at the top of the uterus that lead to the right and left Fallopian tubes. After a sperm fertilizes an egg, an embryo is formed which travels from the tubes into the uterus.


Every month, there is growth of an inner lining of the uterus. This is known as the endometrial lining. If a healthy embryo enters the uterus from the fallopian tubes, then the lining remains in place for the duration of the pregnancy and serves to nourish the baby. If no healthy embryos shows up that month, then the lining is shed as a menstrual period.

One of the most common ways in which uterine abnormalities contribute to infertility occurs when there are fibroid tumors inside the uterus. The fibroid can act the same way that an IUD contraceptive device works in preventing successful implantation. Fibroids that are inside the cavity of the uterus should be removed in infertile patients before proceeding with other types of treatment.



Gratitude extended to Dr. Davide Brunelli for his unique digitally-rendered images of the uterus.