Ovulation Induction Fertility Treatments
Ovulation Induction Fertility Treatments
Richard Paulson (Chief, Division of Reproductive Endocrinology and Infertility, USC) gives expert video advice on: What is "ovulation induction"?; What is "clomiphene citrate"? and more...
What is "ovulation induction"?
One of the main causes of female infertility is the lack of ovulation. Ovulation is a very complicated cascade of events that we take for granted, like so many things in the world, that results in the production of an egg in the woman's ovary, and then a release of that egg so that the egg can be picked up by the fallopian tube and then be fertilized. If this is not happening, we can augment the process by stimulating the ovary to release the egg.There are two general classes of medications that are available for this. One class of medication stimulates the body to make more of a particular hormone called FSH, follicle stimulating hormone. The body that makes the FSH, and the FSH stimulates the ovary to cause ovulation to occur. These medications are typically given in pill form, and they consist of clomiphene or Clomid, tamoxifen. There are the aromatase inhibitors. All of these drugs work the same way. They are given orally, they fool the body into thinking there is less estrogen than there should be, and the body makes more FSH, and causes the woman to ovulate. The majority of women with a condition such as polycystic ovary syndrome, PCOS, will ovulate in response to these oral agents. However, if these do not work, we have to move on to injectable medications. Injectable medications essentially are injectable FSH, follicle stimulating hormone, which is the hormone that stimulates the follicle to grow and then to release the egg. Injectable FHS can be given in a variety of doses, again, to help the ovary produce the egg. The trouble with FSH injections is, first of all, they are expensive. The woman has to take daily injections, and it's quite difficult to control the production of a single egg. Most commonly, we get the production of multiple eggs. This is good if you're doing high-tech fertility, but it's not so good if you're doing ovulation induction, where you really don't want the woman to have more than one baby at a time. So it's pretty tricky to control the dose just right to get her to ovulate that single egg. For this reason, that patient is required to have ultrasounds, blood tests, and so on, to monitor her response in the ovaries, whereas the orally active agents like clomiphene or tamoxifen typically do not require that type of monitoring. The patient can take the pill at home and then simply have intercourse at the time of ovulation.
What is "ovarian hyper-stimulation syndrome" or "OHSS"?
Ovarian hyper-stimulation syndrome is really too much of a good thing. The good thing is a fertility medication that causes the ovary to produce follicles. Of course, that fertility medication contains a hormone called FSH, follicle stimulating hormone, and if you get too much of it then you get too many follicles being too stimulated, and therefore producing too many eggs. In a situation like that, after the ovulation occurs, what's left over in the ovary (which is normally called a corpus luteum) is now so plentiful, and there are so many of these corpora lutea, that they produce some substances in the body which cause a really bad PMS. So, I tell patients, "If you have one egg and you ovulate one, then you'll have a certain amount of PMS. Now, imagine that you've just produced 20 or 30 of these eggs. Then you'll have that same PMS times 20 or 30." So, that would be where the same kind of bloating and the same kind of symptoms that a woman would normally have, with abdominal pain and fluid retention and so on, is amplified 20 or 30 times. This is why ovarian hyper-stimulation syndrome causes fluid retention, lots of abdominal pain, and in some cases fluid shifts. In severe cases, the patients can be quite nauseous and sometimes cannot keep down fluids, and we have to admit them to the hospital for IV fluid hydration. However, typically the syndrome passes on its own about two weeks after ovulation, and there typically are no long-term consequences.
What is "clomiphene citrate"?
Clomiphene citrate, commonly abbreviated "Clomid" because that was its first trade name, is one of the first fertility medications that was available on the market. It came on the market in the 1960s, and it is a medication which acts a little bit like an anti-oestrogen. So, it fools the body into thinking that there is not enough oestrogen in the circulation, and the body responds by making additional follicle stimulating hormone, or FSH, and this additional FSH stimulates the ovary to produce eggs and to ovulate. Now, Clomid is not very good for producing many eggs; in other words, it's not very good for bringing the balance towards producing, let's say five, or eight, or even ten eggs in the ovary. It's good for restoring a balance that's missing. For this reason, Clomid is commonly used in women who have polycystic ovary syndrome (PCOS) or other conditions where they are not ovulating. It is the simplest drug, and the first one, that we would typically use in a fertility setting.
What is a "human menopausal gonadotropin" or "HMG"?
Human menopausal gonadotropin (abbreviated "HMG") is an injectable fertility medication and it was the second one that was developed historically. It also came on the market in the 1960s. It basically contains follicle stimulating hormone or FSH and it also contains a second hormone called luteinising hormone or LH. A combination of FSH and LH will stimulate the ovary directly to produce follicles; those are the hormones that normally do this in the body. So, here is a way of directly stimulating the ovary without depending on the body to produce those hormones. In women who have pituitary failure or a variety of more severe forms of anovulation, as long as the ovary is functional, that ovary can be made to ovulate with the use of HMG or a combination of FSH and LH. In this day and age, HMG is increasingly being replaced by the individual hormones administered by themselves or in different combinations because we now know that FSH by itself is enough, and LH can sometimes be helpful, but you don't always need to have them in a fixed combination of one-to-one like they are in HMG.
What is a "follicle-stimulating hormone" or "FSH"?
A follicle-stimulating hormone (abbreviated to FSH because follicle-stimulating hormone is a mouthful) is the basic hormone produced in the body by the pituitary gland that stimulates the ovaries in a woman and the testicles in a man. It is FSH that rises during puberty and then stimulates the ovary or the testicles to produce either the female hormone estrodial or the male hormone testosterone and makes us go through puberty and makes us look like men and women. And of course, later on in life, FSH is necessary to continue the production of eggs in a woman or sperm in a man. And FSH can be given in the form of an injectable medication if it's lacking from the body, in order to restore ovulation or in order to increase sperm production in a man. So FSH is the basic fertility hormone in the body that controls reproduction, controls the production of the egg and sperm, and controls the function of the adult ovary and testicles.
What is a "gonadotropin-releasing hormone" or "GnRH"?
Most hormone-producing glands in the body are controlled from the pituitary gland. For example the thyroid is controlled by TSH, thyroid-stimulating hormone; and the ovary and the testicle are controlled by FSH, follicle-stimulating hormone. These are all produced by the pituitary. How does the pituitary know when to release these? We come to the releasing factors, and the gonadotropin-releasing hormone, GnRH, also which used to be called LHRH, or luteinizing hormone releasing hormone. These are releasing hormones or releasing factors that come from the brain and are stimulated and delivered directly to the pituitary gland so that the pituitary gland produces FSH and LH, luteinizing hormone, and that then stimulates the ovary in the woman and the testicle in the man. A good way to think of this is when you think of stress as affecting reproductive function, how does that happen? So, stress affects the central nervous system. The central nervous system says “I'm under stress; I better not allow reproduction to occur.” The brain stops the production of GnRH. As a consequence, the pituitary doesn't make any FSH or LH, and as a consequence, the ovary doesn't work, and the testicle doesn't work. And we have lack of reproduction so, if you will, early on in evolution, when our ancestors roamed the wild plains, if there was not enough food, and everybody was hungry and under a lot of stress, that would have been a bad time to have women become pregnant, and so nature chose to put this system into place so women would not ovulate and become pregnant at an inconvenient time. So GnRH comes from the brain, and stimulates the pituitary. The pituitary makes FSH, and that stimulates the ovary, and that makes reproduction go around.
What is "human chorionic gonadoptropin" or "hCG"?
Human chorionic gonadoptropin, abbreviated to HCG, is the basic hormone involved in pregnancy. HCG is the hormone measured in the urine in a home pregnancy test and you can measure it in the serum too. It is used in the treatment of infertility, because HCG resembles another hormone called Luteinizing Hormone, LH, as it turns out that LH is very difficult to work with. It has a very short half life and is cleared from the circulation very quickly. For this reason, we use HCG to trigger ovulation or to help control the hormonal balance in a patient who's trying to become pregnant, but fundamentally HCG is a hormone of pregnancy and so if you pick it up in the urine, it generally means that the patient is pregnant. It's important to realize that if the HCG is used as a fertility medication, that it sticks around in the circulation for up to two weeks, so you can't take a shot of HCG then do a home pregnancy test then if it's positive think that pregnancy has occurred, because you may just be measuring the hormone that you just injected.
What is "metformin"?
Metformin is a diabetic medication. It is used to lower insulin levels and to improve glucose balance in diabetic patients. It so happens that a fair proportion of women with Polycystic Ovary Syndrome, PCOS, have something called insulin resistance, which is a form of diabetes - a form of intolerance to glucose. In these women, high levels of insulin in the circulation stimulate their ovary to produce excess male hormone and make their ovary not ovulate. If women with PCOS take Metformin and it lowers their insulin level to a normal level, many of them will start to ovulate, many of them will find that their hormone level has been reestablished. Metformin is a wonderful medication, and we've been using it for PCOS for some time now. It's wonderful for restoring hormone balance without actually having to use direct stimulation of the ovary.