infertility

Does marijuana cause infertility?

Marijuana and fertility: Princeton IVF blog
Marijuana effects on fertility and pregnancy

All across the country, and likely soon in our state of New Jersey, recreational marijuana us is likely to become legal in more and more places. That means that more couples than ever who are trying to conceive will be users. If you are one of them, should you be concerned?

Here is what we know now:

Does marijuana affect a woman’s fertility?

We know that pot can affect a women’s hormones and her menstrual cycle. Ovulation problems which are related to hormone imbalances are a very common cause for female infertility.

Does marijuana affect a man’s fertility?

The main test fertility doctors use to diagnose male infertility is a semen analysis. We have known for some time that marijuana can have an adverse effect on the most important things we check for in a semen analysis, the number of sperm present (the count), how well they are swimming (motility) and the percent of the sperm that are normally shaped (morphology). We also know that exposure to active ingredient in marijuana THC can cause the breakage of chromosomes and abnormalities in a methylation, a natural chemical process which is responsible for how the genetic material is expressed in the body. Again, we do not know if this directly harmful to a man’s ability to father children or may affect the health of those children.

Is marijuana safe for my baby once I am pregnant?

If you believe the studies in animals, marijuana is not safe for pregnant moms to take. Rats whose mothers were exposed to marijuana in utero were more likely to have cognitive and memory problems in multiple studies. We do not know if this is the case in humans though. Keep in mind that a century ago, alcohol was thought to be safe in pregnancy and it was even used by doctors as a treatment for premature labor. We know now that alcohol causes very specific and severe birth defects when taken during pregnancy.

Is marijuana safe to take when I am breastfeeding?

THC can be found in the breast milk for days after use. Whether this poses any risk to a newborn is not known.

What about extracts that are sold at dispensaries?

No one knows for sure if these preparations are more safe or less safe than whole marijuana smoked or eaten.

So, do I need to be concerned?

No one can say definitively that marijuana use is dangerous during pregnancy nor can it be said to be definitively safe. There are however lots of red flags that raise concern. Most prudent doctors will advise that you and your partner consider avoiding pot if a baby is in your near future

Melatonin and fertility

Melatonin and fertility: Princeton IVF blog
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What is melatonin?

Melatonin is a hormone that is produced in the pineal gland, at the base of the brain. It is involved in the regulating your natural circadian rhythms of sleep and wakefulness. It is considered a “dietary supplement” by the FDA and is available over the counter at pharmacies and vitamin stores.

What is melatonin used for?

Many people find melatonin useful to help them sleep and take a pill (typically 3 mg) at bedtime. It is often helpful for insomnia, for those with unusual  work schedules, overcoming jet lag and to help blind people who do not experience the light and dark cycles. It has also been tried for a number of other medical and psychiatric disorders.

Why would melatonin affect fertility?

Melatonin has been known for sometime to the influence reproduction in some animals so it is not a long shot to think it might affect humans. In one study, they found that the follicular fluid, the liquid that surrounds the eggs and is extracted during an IVF procedure, contains high levels of melatonin.

Is there any evidence the melatonin may help?

There is some research that show eggs retrieved from IVF are more likely to fertilize, produce higher quality better looking embryos, and are more likely to implant. The problem with these studies is that oftentimes they are given along with other supplements (folic acid, inositol and antioxidants) that have been shown to help fertility. Also, just taking a pill or supplement that you think will help you, will help even if it does not contain any active ingredients. That is called the placebo effect. The bottom line is that we do not know.

What about melatonin for men?

There is some evidence that melatonin may lower sperm counts and motility (the percent of sperm that are swimming). For that reason, it is a good idea for men trying to father children to avoid taking melatonin.


Should we try Femara first?

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For years clomiphene has been the main medication that fertility doctors and obgyns use to help women with polycystic ovarian syndrome and irregular cycles to get pregnant

That may be starting to change. In fertility practices such as ours, we have switched to a different drug, letrozole, also known by the brand name, Femara.

What is Letrozole?

Letrozole is a medication that blocks an enzyme in the body that converts testosterone into estrogen. It causes the estrogen levels to drop which lead to the pituitary gland to produce more of a hormone called FSH. FSH (follicle stimulating hormone) is the hormone the causes the eggs to start growing. By doing this, letrozole stimulates ovulation The most common use for letrozole is to help women with breast cancer reduce their risk of recurrence.

Why would you want to use letrozole instead of clomid?

Stimulation with letrozole results in fewer eggs than clomiphene, resulting in fewer multiple births. It is also less likely to cause the side effects of hot flashes and mood swings that are common with clomid.

So, what do the experts say about Femara?

The American College of Obstetrics and Gynecologists has endorsed letrozole as first line treatment for women with PCOS and infertility.

 

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.

So how accurate is my fertility app?

Fertility apps for the iphone and android: Princeton IVF blog
Do fertility apps work?

Many couples trying to get pregnant use them, but do fertility apps for the iphone and android devices really give you valuable information?

As a fertility specialist, my patients are always sharing with me information they learn about their menstrual cycles and their fertile windows from apps on their cell phones. Knowledge about one's body is always a good thing to have, but are these apps really helping couples get accurate information?

To answer this questions, doctors at Weill Cornell Medical College in New York looked at whether these apps (and websites which give out similar information) actually properly inform normal fertile women with regular cycles on the correct days to try for a baby. What they found was a bit disappointing.

While fertility apps were able to select the most fertile day of the cycle, they were quite frequently inaccurate on advising women about their "fertile window."

The apps were not a total bust. Couples who followed the apps advice were not putting their chances of having a baby in peril, even if the app's advice was less than optimal. The iphone has still not replaced the advice of your fertility doctor or gynecologist, at least not yet.

Eggs and fertility after menopause?

Making Eggs after Menopause: Princeton IVF blog

Researchers in Greece report being able to generate eggs from women who have already gone through menopause.

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Doctors in Greece may have found a way to make postmenopausal women grow eggs.

As reported in the New Scientist, fertility researchers have been looking into a new way of potential of helping women in menopause continue to produce eggs. As a women ages, the number and quality of her eggs inevitably declines. By the average age of menopause at age 51-52, there are relatively few eggs left in the ovary, and those that do remain, generally are of such poor quality that ovulation just simply ceases. When this happens, fertility disappears, menstrual periods stop and the symptoms of the lack of estrogen such as hot flashes and vaginal dryness get worse. These symptoms of menopause actually start years before the periods stop but the potential for pregnancy, even if it small, remains.

What if there was a way to reverse this? With this in mind, a team in Greece tried using something called platelet-rich plasma to see if it was possible to regenerate eggs. Platelet rich plasma (PRP) has been used with some success to try and regenerate injured bone and muscle. Among other things, it contains a mixture of growth factors, chemicals found throughout the body that are involved in the natural processes of inflammation and tissue repair. The idea was to try to use the PRP to regenerate ovarian tissue and somehow activate the dormant eggs to grow.

Regenerative medicine for reproductive medicine

The researchers did find some success, and a number of these women did begin to ovulate again. In one patient, they were even able to harvest and fertilize some of these eggs through IVF. The embryos were frozen for later use, so it is unknown whether this procedure can actually result in a pregnancy.

There are still lots of unanswered questions before we can consider this an option for infertile couples in menopause, early or otherwise. We know that the eggs are generally of poor quality in women in their late 40's and when there is fertilization that embryos are generally unhealthy. These embryos rarely implant, and when they do the risk of miscarriage and genetic disorders such as Down Syndrome is quite high. It is not uncommon for women in above 45 to produce enough eggs to do IVF, but it is uncommon that any are good enough to result in a healthy pregnancy. Would the eggs from PRP be any different?

While it is possible that the PRP may improve the quality of these eggs to the point where they can result in a healthy baby, it is just as likely (if not more so) that they they will not. We don't know if the center that reported this data will be able continue to get patients to respond as time goes on or if other fertility clinics will be able to replicate these results. We also do not know if the benefits are short acting or long term, and if they are long acting what the implications are for these patients. Does it mean that a 60 year old can now conceive on her own or how will the continuation of menstrual cycles beyond the natural time affect a woman's risk of diseases such cancer or heart issues? The implications, both medical and ethical, could be enormous.

At this point, it is still just an interesting idea. Still, the prospect of being able to restart a menopausal ovary is intriguing to fertility specialists and their patients.

Celiac disease, fertility and pregnancy

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Is there a link between celiac disease, infertility and pregnancy complications?

Celiac disease is a relative common disorder of the gastrointestinal tract caused by an allergy to gluten, a protein commonly found in wheat and other grain products. Like many other diseases, it what we call an autoimmune disorder, a disease in which the body's immune system attacks the person's own normal cells. Treatment of this disease rarely requires any drugs and almost always is helped by changing one's diet to a gluten-free one. The disease is also known as celiac or nontropical sprue, or gluten-sensitive enteropathy. Women (and men) who suffer from celiac disease may have symptoms such as:

  • abdominal bloating and pain
  • diarrhea or constipation
  • weight loss
  • fatigue

Studies on Celiac disease have also reported higher rates of infertility, miscarriages and menstrual problems among women with the disease, and then once pregnant, higher rates of a number of pregnancy complications such as low birth weight babies. It has even been reported to affects male fertility.

So, does this mean the Celiac disease causes fertility and pregnancy problems? Not so fast. Many of these studies are really too weak and small to draw any real conclusions. Still other studies fail to show that Celiac disease causes any reproductive issues. At this time, issue is far from settled.

For those looking to find a reason for their otherwise unexplained infertility, this may not be for the answer. However, for those who are having trouble getting pregnant and have lots of gastrointestinal symptoms, it may not be a bad idea to ask your doctor about getting tested for Celiac disease.

 

Soy and fertility

Are soy products good or bad for your fertility?

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Soy products such as soy milk and tofu are high in protein and have become popular for their reported health benefits. So, why the concern?It turns out that soy products also contain chemicals called phytoestrogens. These phytoestrogens are chemicals found in plants that look and act like estrogens, the "female" sex hormones that both women and men produce naturally.  It is commonly believed (but not universally accepted) that these phytoestrogens may have health benefits such as reducing the risk of cardiovascular disease and taming the symptoms of menopause. One of the main concerns over the use of these "dietary supplements" is that if they act like estrogens, they may very well carry the the same risks as taking estrogen pills like Premarin and Estrace.

 So, how does this tie in with fertility issues? One of the key ingredients in birth control pills is a type of estrogen (commonly ethinyl estradiol) so it should come as no surprise there may that taking soy products could potentially be a problem for women attempting pregnancy.

With that in mind, researchers at Harvard's School of Public Health, looked at women undergoing IVF treatment to see if the use of soy products had any effect on the pregnancy rates. The results were somewhat surprising. IVF patients taking soy supplements were actually more likely to get pregnant. While the study was small and limited, and it is certainly to early to encourage women doing IVF to take in more soy products, it does appear to be reassuring for those trying to get pregnant and don't want to stop the soy milk and tofu.