Should we try Femara first?

letrozole-femara-fertility

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 mediterranean diet and fertility

Mediterranean diet and fertility: Princeton IVF blog
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As a fertility specialist, one of the most common questions I get is about diet, what can changes can I make in my diet to help me get pregnant?

For some patients, particularly those with PCOS that answer is relatively simple. It well know that a diet high in protein and low in carbohydrates helps women with polycystic ovaries to conceive. 

For other women with infertility, the answer is less clear.

A recent study from Greece, looked at women who self-reported at following a "mediterranean diet." Women on a Mediterranean diet had a higher pregnancy rate that those who did not.

Does this prove that a diet in low in animal fats and high in vegetables and fruit can help you get pregnant? No, but it does suggest a health diet low in carbs and red meats may help your chances of having a baby.

Acupuncture and Infertility

Acupuncture and IVF pregnancy rates: Princeton IVF blog
 New study sheds doubt on whether acupuncture really helps IVF pregnancy rates

Lots of women seek out acupuncture to help them get pregnant, but does it really help?

Complementary and alternative medical treatments have become very popular for treating and preventing diseases, including the treatment of infertility. This may including vitamins and herbs and treatments such as acupuncture.

A number of researchers have found that acupuncture does improve fertility, at least in women who are undergoing IVF treatment, but some have not.

In order to figure out what it really going on, a group of doctors in Australia studies 824 women undergoing in vitro fertilization at their clinic. Half got real acupuncture (meaning the needles were placed in the right place according to acupuncture practice guidelines) and in the other half of patients, the needles were placed in locations that were not expected to have any effect. We call this last treatment "sham" acupuncture. They compared outcomes between the two groups.

They found out that women who had sham acupuncture were no more likely to get pregnant than those who had acupuncture done correctly. The pregnancy rates in these two groups were almost identical.

So what does this mean?

It is likely that acupuncture does not improve the chances for success with IVF, and if it does, the benefit is likely very small.

Were there any benefits to acupuncture in these women?

Yes. Women who received acupuncture were more relaxed and had a better sense of well being that those who had only sham acupuncture. This is not a small issue since IVF treatment is very stressful to the couples who are going through it.

Knowing this, should I still get acupuncture done?

Acupuncture is safe and comforting even if it may not be effective in IVF treatment. Other than the cost if it is not covered, there is really no risk to trying it.

Fewer complications in IVF pregnancies?

 New research suggests IVF pregnancies could have lower rates of some complications

Surprisingly, some complications might actually be less common in pregnancies that result from assisted reproductive technology such as IVF

This seems to go against what fertility doctors, obgyns and midwives have been telling their patients for years, namely that women with IVF pregnancies are more likely than "regular" pregnancies to experience pregnancy complications.

What complications were actually less common in IVF pregnancies?

A group looking at IVF outcome data submitted through the Society for Assisted Reproductive Technology (SART) to the Centers for Disease Control (CDC) found that risk of perinatal mortality (the risk of stillbirth or newborn death) in very premature births was lower in women who conceived with IVF than those who did not. They found this to be true with both single births and multiple births (twins triplets, etc.) This informations was recently presented at the American College of Obstetricians and Gynecologists.

Does this mean getting pregnant with IVF is actually safer than getting pregnant on your own?

Probably not. Women who conceived with IVF were less likely to lose a premature baby than those who got pregnant on their own. We have no idea why this is the case. It could be due to more careful prenatal care with IVF pregnancies, or a higher socioeconomic level in couples doing IVF, rather that a results of what is actually going on with the pregnancy. 

Why is this surprising?

There are many studies show a higher rate of complications in pregnancies that result from assisted reproduction such as IVF, and some others that show no effect. It was surprising to find out from such as large database, that at least one serious complication was less common.

Can menopause be reversed with stem cells?

Restoring fertility with stem cells: Princeton IVF blog
 New research suggests bone marrow stem cells could be used restore estrogen and fertility in women with early menopause.

It may become possible in the near future

Women who suffer from premature menopause, also known as primary ovarian insufficiency (POI) or primary ovarian failure (POF) have either run out of eggs or no eggs capable of being stimulated.

This can occur for a number of reasons but early menopause causes 2 major problems for women who suffer from it. One is infertility, and this type of infertility can usually only be successfully treated with donor egg IVF. The other problem is hormonal. With the depletion of ovarian follicles, levels of reproductive hormones, especially estrogen, drop dramatically. The low levels of estrogen can cause a number of problems including vaginal dryness, difficulty with intercourse, hot flushes, bone loss and loss of sleep to name a few.

So, if there was a safe way to restore eggs to an ovary that has shut down prematurely, it might be a great advance in women's health care.

With that in mind, the ROSE trial was undertaken. The researchers injected cells from the bone marrow, which is rich in stem cells into the ovaries in an attempt to help regenerate new eggs.

Obtaining cells from the bone marrow is a fairly routine medical procedure and injecting substances into the ovarian is also not a new procedure. What is new about this is combining the two and using stem cell to restore ovarian function.

The few patients in the trial had an increase in the size of their ovaries and higher estrogen levels even a year out of from the procedure.

It will still take time and more studies to determine how safe and effective stem cells from the bone marrow are at restoring functioning ovaries and fertility to women with premature menopause / POI, but the results so far are encouraging. 

 

Celebrities having babies over 40

Pregnancy in your 40s- how realistic is it?: Princeton IVF blog
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The media shows plenty of Hollywood stars having babies in their 40s, but are they telling the whole story?

For many it is exciting to hear about the celebrities they adore having babies. Like many women in the society at large, many celebrities have chosen to delay having children for a variety of reasons. It should come at surprise, then, that many of the celebrity moms depicted in the magazines are in their 40s.

Knowing how women trying to start a family (or growing her current family) as they get older face an uphill battle,  are the media who cover these stories doing a disservice to women's reproductive health?

To answer this question, researchers at New York University looked at all the issues of 3 popular magazines widely read by women of reproductive age over a 4 year period.

This is what they found:

  • There were 1,894 references to pregnancy or fertility
  • 1/3 of the issues had cover stories related to fertility
  • There 240 celebrities, who averaged age 35
  • Only 2 articles on 40+ year olds using donor eggs
  • There were 10 stories about adoption and 5 about using a gestational carrier. Not one of these mentioned that they had previously suffered from infertility

It is understandable that a celebrity (or anyone else for that matter) would not want to share the very personal details of what it is like to go through fertility testing and treatment.  Still, the stories presented to the public are far from complete. While there is nothing that appears to be inaccurate in the articles, they present an unrealistic view of normal fertility after 35.

Modern fertility treatments have revolutionized the ability of couples suffering from infertility to get pregnant, but it has not been able to eliminate reproductive aging. Implying that waiting to have children is not harmful to your fertility through human interest stories is doing a disservice to women. 

Is the traffic outside affecting your chances of having a baby?

Living near a highway and IVF pregnancy rates: Princeton IVF blog
 Women who live in high traffic areas are more likely to miscarry

Living in a high traffic area may hurt your chances for success with IVF

Research from Harvard presented at the annual meeting of the American Society for Reproductive Medicine suggests that women with a higher exposure to automotive traffic have lower IVF success rates than other women.

The researchers looked at 660 IVF cycles done over a 14 year period and compared their success rates to  how far they lived from a class A roadway. A class A roadway means an interstate, state or US highway. 

Women who lived more than a kilometer (0.6 miles) from a major roadway were 70% more likely to have a baby than those who lived within 200 meters (about 2 football fields) of a major roadway.

Interestingly, both groups of patients had similar pregnancy rates, but the those who live closed to the highway were more likely to miscarry.

Does this mean moving to a low traffic area will improve your chances  of having a baby?

Not necessarily. It does show what we already know, that the environment we live in and the air we breathe plays a role in reproduction, as it does in other aspects of health.

 

When is it time to give up on IVF?

 Couples continue to get pregnant with IVF put 8 cycles.
When is it time to stop IVF: Princeton IVF blog

Any couple who has gone through IVF knows what a rough and wild ride it can be, both physically and emotionally. For that reason, many couples give up on IVF early on, perhaps too early.

Why do women drop out of IVF treatment?

The reasons why women quite IVF are usually financial, when their insurance coverage or access to funds to pay for treatment run out, or emotional, when the thought of going through another cycle and the prospect of all the drugs, office visits and prospect of disappointment becomes overwhelming.

But, what happens to couples who persist and continue to go through IVF treatment cycles?

Fertility doctors in Bristol in the UK, sought to answer that question and what they found was encouraging. In their program, 1/3 of patients conceived on the first IVF cycle. In the next 3 cycles (1-4) the pregnancy rate was about 20% per cycle. While the rates were lower in cycles 5 and 6, they were not zero. Pregnancies continue to happen.

After 6 cycles of IVF, the cumulative pregnancy rate was 68%. In women between 40 and 42, there were successful pregnancies through the 9th cycle.

We've failed a few cycles of IVF. Should we give up?

Only you and your partner can answer that question. IVF tends to be more successful on the first round, but successful pregnancies do continue to happen with repeated attempts, sometimes even when it seems futile.

 

Do I need to have a period before starting Clomid?

 It may be OK to start clomid without a period.   

It may be possible to ovulate without a period.

For many couples suffering from infertility, the treatment journey starts with Clomid (clomiphene). These fertility pills help to stimulate ovulation, and when used properly, are safe and effective as a first line treatment for many couples.

One of the more frustrating parts of about taking Clomid is having to wait for a menstrual period to start the medications.

Traditionally, Clomid is started on the 3rd or 5th day of the menstrual cycle, and it is not uncommon for doctors to proscribe progesterone-like medication to bring on the period before starting fertility drugs. If you are seeing an obgyn physician for your fertility treatment and your cycles are irregular, this is likely what will happen.

It turns out it is no longer necessary to have a period in order to start fertility drugs.

Fertility specialists have adopted this new way of thinking after a article came out a few years ago, suggesting the having a period is not necessary in order for fertility pills to be successful.  Not only that, but the chances for success may even be lower if medications are used to bring on the period. This is referred to as the "stair step protocol." So, what does this mean?

The stair step protocol means less time to make you ovulate and a shorter time to conception.

So, why does my doctor not use clomiphene that way?

Most obgyn doctors have been trained to use Clomid in the traditional way. Fertility specialists tend to be more current on the latest treatments and more likely to offer the stair step.

Can the stair step be used with other fertility drugs?

In our practice, we routinely use letrozole (Femara) in place of clomiphene with the stair step and it works just fine. Injectable fertility drugs can also be started without a period, but those treatment cycles are different.

Does this mean we can start clomiphene at any time?

No. Your doctor will need to determine that you are not pregnant and did not ovulate already before starting fertility drugs. Using these drugs as the wrong time of the cycle can cause more harm than good.

 

Could your fertility be a gauge of your health?

 Infertility may mean health risks in the future

Research suggests that women with infertility may be at higher risk for health problems in the future

As a fertility specialist, I hear this all the time. I am healthy and take good care of myself, so there should be no reason I am not be getting pregnant. Naturally, we go on to discuss how one's fertility can be quite separate from your general health, as is quite often the case. Perhaps, though, that is not completely true.

A study out of the University of Pennsylvania and the National Cancer Institute followed women long term for health issues. 

They were mostly followed for cancer related issues, but were also asked about a history of infertility as a part of the study.

What they found though was interesting, including:

  • overall, women with a history of infertility had a 10% risk of dying over the 13 year study time
  • women with a history of infertility had a 20% increased risk of dying from cancer
  • women with a history of infertility had a 44% increased risk of dying from breast cancer
  • women with a history of infertility had a 70% increased risk of dying from diabetes, even though they were no more likely to have diabetes
  • uterine and ovarian cancer were no more common in women with a history of infertility

Does these mean the infertility causes poor health? Probably not, but it does mean that infertility could be sign of underlying health issues.

It means that women with a history of infertility, whether they were treated or not, whether they were successful or not, need to pay attention to their general health. 

 

 

Should I stop alcohol before pregnancy?

 Moderate alcohol does not harm fertility but not safe during pregnancy.

Many women stop all alcohol when starting to attempt pregnancy, but does it really help?

Probably not. Research suggests that moderate alcohol intake will likely not harm your fertility.

Before we go any further, this means prior to pregnancy. No one including your doctor or midwife can reassure you that alcohol is safe to take in any amount during pregnancy, and that includes the week that you are pregnant before the pregnancy test comes out positive.

Anyhow, getting back to the story, researchers in Denmark compared a group of women who more moderate drinkers (between 1 and 14 glasses of wine per week) to another group of women who did not drink at all while attempting pregnancy. The researchers did not find any difference in the chances for pregnancy between the 2 groups. The same was not true for heavier drinkers. Those who drank the equivalent of 2 bottles of wine per week or more were actually less likely to conceive.

So what this mean for drinking alcohol when trying to conceive?

According this study, light to moderate alcohol likely does not affect your chances of having a baby, but heavy alcohol consumption likely does.

Can I drink when I'm trying to get pregnant?

In moderation, alcohol consumption before a pregnancy implants in the uterus is fine.  A pregnancy implants about a week before you expect your period, and it is impossible to say if it is safe to drink from that time on.

What about alcohol during the rest of pregnancy?

Heavy and moderate alcohol are well known to cause serious birth defects. Ask your doctor or midwife. They will almost certainly agree.It is not clear whether have an occasional glass of wine will increase your risk of birth defects or not. In the absence of information to reassure our patients, most of obstetricians and midwives will advise against it.

Live birth after uterine transplant

Live birth after uterine transplant: Princeton IVF blog

Doctors at Baylor University deliver the first US baby born following uterine transplantation

A few years back, doctors in Sweden performed the first successful uterine transplant. Several academic fertility centers in the US have tried to replicate this here, and doctors at Baylor announced they were the first to do so.

Why would one want to transplant a uterus?

It is impossible to carry a baby without a uterus, also known as the womb. The early embryo implants itself into the wall the uterus about a week after conception and through the placenta and umbilical cord, its interface to the uterus, the fetus gets all of the nutrients and oxygen it needs to grow and even to survive.

Some women are born without a uterus (such as in the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome), some have scar tissue in the uterus and others have had their uterus removed (a hysterectomy) for fibroids, cancer or some other reason. While there have been many many cases of ectopic pregnancies, where a pregnancy implants outside the uterus, these pregnancies nearly always need to be terminated early on since they can result on the death of the mother, and almost never results in a live birth of a baby. There is also interest in using a transplanted uterus in transgender women.

Are there alternatives ways to have baby without a uterus?

Currently, there is a very effective way of having a baby without a womb, and it is called Gestational Carrier IVF.  The eggs are harvested from the intended mother, sperm is collected from the intended father, and fertilization is performed in the IVF laboratory. The embryos are grown and transfered into the uterus another woman, referred to as a gestational carrier after her uterus is prepared for pregnancy using hormonal treatments. This can be costly (but much less so than a uterine transplatation), is illegal in some states and most importantly, the pregnancy is carried and delivered by someone else other than the intended mother.

How is a uterine transplant performed?

The uteri used for transplantation can be obtained from living donors or women who have recently passed away and offered their organs up for donation. Using an open incision (laparotomy in medical jingo), the donor uterus is attached the various blood vessels to ensure it has good supply and to attached to nearby structures to hold it in place. It is not attached to the fallopian tube.

How does a woman get pregnant after uterine transplantation?

IVF (in vitro fertilization) is required to achieve pregnancy since without a connection between the tube and uterus, pregnancy would otherwise be impossible. In years past, fertility surgeons, connected fallopian tubes to the uterus, but that operation has been abandoned since it rarely worked. IVF bypasses that problem and offers the best chance for pregnancy.

Are more uterine transplant babies coming?

The doctors at Baylor have another woman pregnant after uterine transplantation and IVF, a few more attempts planned. A number of women undergoing the procedure have not been successful. Other centers are trying this as well, but the costs are so high and it is not covered by insurance, so it not clear how widespread this will become.

Twin sons from another mother: a true story

A gestational carrier with twins finds out one of the twins she was carrying was her own

Surrogate mom gives birth  to twins boys, but one only was from her IVF cycle, the others was her own.

How is that possible?

When a couple uses a gestational carrier (what most people think of a surrogacy), embryos are produced from the eggs from the intended mother and sperm from the intended father. Sometimes the eggs or sperm are from a donor instead. Regardless, the embryos are placed in the womb of the gestational carrier, the woman who will carry the pregnancy and give birth for the intended parents. The carrier will take hormones to help prepare her uterus for pregnancy. This process has been done for years by fertility specialists, is highly successful and despite its complexity usually goes off without a hitch.

Not this time though...

A California woman agreed to be a gestational carrier for another couple. They did a form of IVF and the procedure seemingly went well. The carrier became pregnant and on ultrasound they saw twins.  Since one embryo was transfered, the doctors naturally assumed the twins were identical. The pregnancy went well, the twins were delivered by cesarian section and went to live with the intended parents.

A month later, genetic testing revealed that the twins were not identical, and that the child's genetic parents were actually the gestational carrier and her husband.

How could this happen...

In a process called suprafecundation, a women who is already pregnant, or this case, in the process of becoming pregnant, can ovulate again.

When this happens, a woman who is pregnant would conceive a second pregnancy when she ovulates a month later. So, the second baby would be due a month later than the first. This type of event is exceedingly rare, but it looks like this is happened here, but on a shorter time frame.

 

Is treating infertility a crime?

Is treating infertility a crime?: Princeton IVF blog

Irish government proposes draconian new regulations of IVF treatments

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Fertility treatments, particularly IVF have been subject to strict government regulations around the world, but has the Irish government's proposals gone too far this time?

Recently, the Irish government Department of Health has decided to develop a plan to provide IVF treatment for its citizens who suffer from infertility. While this is excellent news, they are also proposing some regulations, that are a bit over the top including...

One can understand their desire to refuse to cover treatments that would be less likely to result in a healthy live birth, but to threaten jail time for doctors and staff for performing IVF. That makes no sense. Hopefully, these absurd regulations are never enacted.

 

IVF no longer covered where it all started

IVF-insurance-coverage-in-UK.jpg

The first IVF baby Louise Brown was conceived near Cambridge, England over 3 decades ago...

Now it turns out that National Health Service in Cambridgeshire will no longer cover IVF treatment in the place where it all began.

It is sad but true according the BBC...

The UK with its single payer government health system, like all other health systems, has limited funds and been forced to make a decision on where to cut. In Cambridgeshire, coverage for IVF was one of those cuts even though ivf treatment is recommended by the nhs' own guidelines.

In the United States, where we have a more fragmented system, some states such as New Jersey where we are located, mandate coverage. While the law remains intact and recently was amended to expand the definition of infertility, health care reform laws such as the Affordable Care Act (ACA, Obamacare) has actually reduced the number of women in our state who are covered for fertility treatment. When faced with multiple mandates, employers and insurers are forced to make decisions where to cut to control their premiums.

While there is plenty of talk these days about advocating a single payer government controlled system, it is not clear that such a change will benefit couples with infertility. While some countries with national health care systems do cover IVF and other treatments, it is often the first item on the chopping block when costs are getting out of control. It is certainly the case in Britain.

For those who advocate for the availability of treatment of infertile couples, be careful what you wish for. Increased access to medical care does not necessarily mean increaseD access to fertility care.

A spoonful of sugar may may the medicine go down, but will it harm your chances for pregnancy?

Sugary drinks, articifical sweeteners and fertility: Princeton IVF blog
sugar-drinks-ivf-pregnancy.jpg

Recent studies suggests that sugary drinks, even those with artificial sweeteners may harm the chances for pregnancy.

Although it is far from conclusive, several recent studies suggest that sweet drinks may have an adverse effect of a woman's chance for pregnancy, including...

  • Harvard doctors found that drinking one sugary drink a day can lower the success rate of IVF by 12% and more than one sweet drink a day by 16%

  • Brazilian researchers found that consuming sugary or artificially sweetened drinks reduced embryo quality and the chances for an embryo to implant. interestingly

Interestingly this effect did not occur with unsweetened coffee.

The reason for this is not totally clear, though we know both obesity and polycystic ovarian syndrome (PCOS), which are both associated with infertility and miscarriage, and associated with changes in how the body handles sugar, can lower the chances for pregnancy.

So, what should I do?

It is a good idea to keep sugary products to a minimum when you are trying to get pregnant, and to minimize artificial sweeteners such as Splenda, Equal or Sweet-and-Low. These sugar substitutes may be just as harmful as sugar itself.

Don't panic. Women who use artificial sweeteners and drink sweet drinks still get pregnant all the time, even if the chances are a little lower. There are many factors that go into your fertility, so it is far from clear that consuming these drinks is actually harms your chances for pregnancy.

IVF for Coral

Saving coral reefs with IVF: Princeton IVF blog

Saving the coral reefs with assisted reproduction

 In vitro fertilization to save Great Barrier Reef and other coral reefs

 

IVF has been used to help couples with infertility for decades but could it now be used help save world's coral reefs too?

Researchers think so. Scientists in the UK, Australia and the US are experimenting with using a technique very similar to in vitro fertilization to help restore the coral reefs of  the world. In turns out that coral are very poor at reproducing  and restoring their populations following environmental insults such as climate change or storms. They are hoping to use techniques similar to those used in helping infertile couples conceive to reseed bleached areas in the reefs.

Only time will tell if this will work.

Will I still be fertile when I am ready to have kids?

Blood test may not predict future fertility: Princeton IVF blog
AMH-to-predict-future-fertility.jpg

Fertility specialists (and obgyns) get this question all the time.

How can I know when my fertility will run out?

Many fertility doctors have recommended checking a test called AMH to see whether a women is approaching the end of her fertility. This is a blood test that we commonly use to determine ovarian reserve, which is a measure of how many eggs are left and how many eggs a woman might expect to be able to make when on fertility drugs, like those drugs taken for an IVF cycle. We know that AMH is fairly good predictor of how a woman will respond to drugs, and to a lesser extent how likely she is to conceive on treatments. This test is now easy to obtain, helpful for counseling and it use has become fairly routine among fertility specialists.

So, if it is good to determine the chances for success in women seeking fertility treatment, shouldn't it be useful in determining which women might have trouble getting pregnant down the line?

It certainly makes sense. Use the AMH to determine which women are starting to run out of eggs, and encourage them to start trying to get pregnant sooner, not delay seeking help with a specialist or even freeze her eggs for the future.

To test this idea, researchers in North Carolina looked at AMH as well as several other markers of aging ovaries to see if they might predict whether a women would have trouble getting pregnant going forward.

It turned out that AMH and the other tests could not predict infertility in the near future, and that the only thing that could predict the chances for pregnancy was age.

The take home message: there is no magic test at this time that can predict your future fertility. The best recommendation is the old recommendation. Don't wait.

Ready to give up after IVF? It's not time to give up.

Many couples with unsuccessful IVFs get pregnant on their own
 Upto a third of couples who failed to get pregnant with IVF may get pregnant on their own.

IVF treatment can be incredibly stressful, even when it is successful. Imagine how difficult IVF can be when it is not? That is likely why so many couples give up after an unsuccessful IVF cycle.

According to reasearchers in the UK, almost a third of couples who are not successful at IVF and stop treatment will conceive on their own, although that might take up to 2 years.

Surprisingly, many of the couples who did conceive this way were not as thrilled as one might expect. Some couples have moved on in their life situations, and others were felt that maybe they never needed IVF in the first place.

Dr. Seth Derman, Inside Jersey Top Doctor

Dr. Seth Derman- a top fertility doctor in NJ
 Seth G Derman, MD, Reproductive Medicine Specialist and Inside Jersey top doctor

Dr Derman named to the top doctor list once again for 2017

The medical director at Princeton IVF and a Reproductive Endocrinologist at Delaware Valley OBGYN and Infertility, Dr. Seth Derman has been named one of Inside Jersey Magazine's Top 2128 Doctors for 2017.

Candidates for the top doctor list are vetted  by Castle Connolly, and nominated and selected by their peers for inclusion in this list.