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The inventor of clomid and his legacy

The legacy of the inventor of clomiphene, Frank Palopali
Frank Palopali invented the fertility drug Clomid.

The story behind the first fertility drug, Clomid.

As the year draws to a close, the newspapers, TV stations and other media outlets will share stories about individuals whom we lost in the past year. We will hear stories about great artists, musicians, athletes, politicians and others, about how they lived their lives and how their life's work impacted our own lives. It is likely these accolades will miss out on someone whose impact on world of reproductive medicine and generations of couples suffering from infertility. That man was Frank Palopoli.

Who was Frank Palopali? 

Frank Palopali was a research chemist at the Merrell Dow Company. He was the leader of the team that developed clomiphene (Clomid) one of the most commonly used fertility drugs in the world. His work in the laboratory started back in the 1950's and first clinical trials of clomiphene were published in 1961. In 1967, Clomid was approved by the Food and Drug Administration and it became available to the public.

So, why was Clomid such a big deal? 

In this age of high tech, highly effective fertility treatments, IVF with genetic testing and the like, it is somewhat difficult to understand why an  inexpensive pill you pick up at Walmart for less than $10 might be such a big thing, but it was a huge breakthrough. If you look back to the world of women's reproductive health care 50 years ago, most fertility treatments were relatively ineffective and more often than not involved major surgery. For instance, the treatment of polycystic ovarian syndrome (PCOS) at the time involved in operation called the ovarian wedge resection. The gynecologic surgeon would make it open incision in the abdomen (similar to a cesarean section) and remove a wedge-shaped portion of the ovary, and then stitch the remaining ovary back together before closing the abdominal incision. Like other major surgeries, recovery from this operation could take weeks or months, but the benefit, if any, was very short term, just a few months afterwards. Additionally, eggs were inevitably lost in the process and scar tissue could develop on the surface of the ovaries, both of which could harm a woman's future fertility.

With the invention of clomiphene it was now possible to treat PCOS with just a pill. It completely revolutionized the treatment of infertility caused by problems of ovulation, and ovulation problems such as irregular cycles are among the most common causes of infertility in women. No longer would costly and invasive procedures be required, at least for most women with PCOS. While future inventions such as injectable fertility drugs, alternative methods of ovulation induction and IVF would bring success to many more people, it all started with the development of Clomid.

Over past nearly half a century since this time, millions upon millions of women all over the world have been able to have children and grow their families because of this invention. The number of couples helped by clomiphene actually dwarfs the number of those helped by IVF.

How does Clomiphene work?

Clomiphene is an anti-estrogen. It is part of a class of drugs called SERMs (selective estrogen receptor modulators) which include tamoxifen (Nolvadex) and reloxifene (Evista), drugs which are used to breast cancer and menopausal symptoms. Clomid works by blocking estrogen, the main female hormone. By blocking estrogen from working at the brain and pituitary gland (the master gland at the base of the brain), it tricks the body into sensing that there is no at there is no estrogen around. As a result, the hormones (FSH and LH) that stimulate the ovary, start to rise. This rise in hormones then kickstarts the process of the egg starting to grow and begins the path towards ovulation.

What are clomiphene's side effects?

It is easier to understand the side effects of clomiphene when you understand how it works. Because Clomid is anti-estrogen, it can cause hot flashes, headaches, breast discomfort and other symptoms that we normally associate with menopause. Because it stimulates the follicles (the cysts which contain the eggs) to grow, it can cause discomfort in the abdomen and increases the risk of multiple births. There are also concerns about whether clomiphene increases the risk of ovarian cancer, though most of the studies suggest it safe that when use for a brief period time. This is another reason to seek out the care of a fertility specialist early in the course of your treatment.

What is clomiphene used for?

The original and most common use for clomiphene is to help women who don't ovulate regularly, to produce and release eggs, become pregnant or hold on to a pregnancy. Clomiphene is also that used to help women produce multiple eggs to help improve the chances for success with insemination (IUI) and IVF. Clomiphene has also been used in men to assist in their fertility. This medication is intended to be used under the guidance of us physician experienced in their use.

How much is the price of clomiphene?

Like any other medication, the cost of clomiphene varies from pharmacy to pharmacy. Generic clomiphene in the typical starting dosing (50 mg) frequently sells for less than $10 at large retailers such as Walmart or Target. In the US, this medication always requires a prescription.

How many days after Clomid do you ovulate?

This a common question without a straight forward answer. Most women will ovulate around day 14 of the cycle, give or take a few days. Since clomiphene is usually taken day 3-7 or days 5-9, that means about 5-7 days after the last pill. However, some women will ovulate earlier, some later or not at all. At our center, we like to monitor everyone on clomiphene to make sure we get the timing right, and not delay pregnancy any longer than necessary.

Clomid success rate- how well does it work?

When used for to help infertile women with irregular or absent menstrual cycles, clomid enables about 80% of women to ovulate when used over a period of time. About half of these women will go on to conceive. This is actually quite good when you realize that natural conception in normal fertile women is only about 20-25%. The success rates when using clomiphene for other causes of infertility (unexplained, male infertility, endometriosis, etc.) is lower. 

Can clomiphene be used in men?

Clomid is sometimes used to treat male infertility, though it is considered an "off-label" use. Since its use and its effectiveness in men is somewhat more controversial than its use in women, it is best prescribed and managed by a urologist with special expertise in male fertility.