Vitamin D is a fat soluble vitamin that is present in a variety of forms but has recently been recognized as playing a critical role in reproduction.  It is essential in the production of sex hormones in the body.  It is thought that a deficiency of Vitamin D may lead among other things to ovulation disorders.

It has been demonstrated that Vitamin D deficient rats had a 75% reduced fertility and a 50% smaller litter size that was corrected with Vitamin D treatment.  In addition, sperm motility in males was reduced in the presence of a Vitamin D deficiency.

A recent study at the Yale University School of Medicine revealed that only 7% of 67 infertile women studied had normal Vitamin D levels and not a single woman with an ovulatory disorder had normal levels.  Nearly 40% of women with ovulatory dysfunction had a clinical deficiency of Vitamin D.

At the American Society of Reproductive Medicine conference this year, a study presented by Dr. Briana Rudick from USC showed that a deficiency of Vitamin D can also have a detrimental effect on pregnancy rates after IVF, possibly through an effect on the[O1] endometrial lining of the uterus.   In her study only 42% of the infertile women going through IVF had normal Vitamin D levels.  Vitamin D levels did not impact the number of ampules of gonadotropin utilized nor the number of eggs stimulated, embryos created nor embro quality.  However, Vitamin D levels did significantly effect pregnancy rates even when controlled for number of embryos transferred and embryo quality.  In this study the pregnancy rate dropped from 51% in Caucasian women undergoing IVF who had normal Vitamin D levels to 44% in those with insufficient levels and 19% in those that were deficient.

Vitamin D deficiency has also been associated with poor pregnancy outcomes including preeclampsia and gestational diabetes

Vitamin D can be obtained for free by sitting out in the sun and getting sun exposure on the arms and legs for 15-20 minutes per day during peak sunlight hours.  The sunlight helps the skin to create Vitamin D3 that is then transformed into the active form of Vitamin D by the kidneys and liver.   An oral supplement is available also in the form of Vitamin D3, with a minimum recommended amount of 1000 IU a day for women planning on becoming pregnant.  For those with clinical insufficiencies a higher dose may be administered by injection.

Many husbands pride themselves in their new found skill with mixing medications and administering injections for their wives. It helps many men who are used to caring for their wives to be in control of administering the medication for them. Successful IVF then becomes something he’s has played a very active role in and related better to the experience, his wife and the resulting baby.

Despite a lack of prior experience, most people can learn to prepare and administer the medication. Whether it is the feeling of “playing doctor” or the knowledge that he is contributing significantly in the process and supporting his wife, most men relate that giving their wives the injections was a positive experience for them and for their relationship.

Along the same line of thinking, accompanying your wife at the time of embryo transfer can be most rewarding. This can be a highly emotional procedure. Your embryo/s is being placed in the womb and at least in that moment many women feel as if they are pregnant. Life may be starting here and it is wonderful to share this moment with your wife. Perhaps you may keep the Petri dish as a keepsake as the “baby’s first crib”. It is an experience a husband and wife are not likely to forget as their first time together as a family. I strongly recommend that men don those scrubs, hats and booties and join their wines and partners as the physician transfers the embryos from the dish into her womb. Nine months later do the same at delivery for memories that last a lifetime.

Dr. Kreiner with Drs. Howard and Georgeanna Jones

In 1987, I completed my Reproductive Endocrinology and Infertility fellowship under  Drs. Howard W. Jones Jr. and his wife Georgeanna Seegar Jones, the two pioneers of in-vitro fertilization in the USA and the entire western hemisphere.

This picture was taken at their house on the Elizabeth River in Norfolk during one of the bimonthly journal clubs.  It was routine for the Joneses to host the journal clubs twice a month during which the entire Reproductive Endocrinology team would discuss interesting cutting edge research in the field.

Learn more about the History of IVF at the Jones Institute here.

According to the Center for Disease Control, reported in the same NY Times issue, thousands of premature deliveries would be prevented resulting in a $1.1 Billion savings if elective single embryo transfer was performed on good prognosis patients. That brings us to regulating how many embryos to transfer as Octomom went through IVF with transfer of six embryos. At East Coat Fertility, we make it cost neutral to transfer only one embryo at a time by offering free cryopreservation, free embryo storage and free embryo transfers until a patient achieves a live birth, all for the cost of a single IVF cycle. Patients are encouraged by this program not to put all their eggs in one basket. Success rates with an elective fresh single embryo transfer with IVF at our program, is 50% and with subsequent frozen embryo transfers it is over 64%. It is possible that East Coast Fertility is the only center in the country doing this. That is the shame of it.

Fertility treatment without IVF is even more hazardous since as many eggs that are developed with treatment may implant and lead to a hazardous multiple pregnancy. In a perfect world, where a patient’s welfare was put before insurance companies, IVF would be a covered service for all people, and the use of fertility medications in an uncontrolled IUI cycle would not be used anymore. In this perfect world, we would also regulate how many embryos are transferred. It is time to put our professional recommendations of the Society of Assisted Reproductive Technology (SART) into law. There is flexibility built into the recommendations taking into account critical factors such as patient age, embryo quality and past experience.

It is not until we discourage the use of gonadotropins without IVF by offering IVF as a regulated covered alternative will we eliminate risky multiple pregnancies. Until then, all of us including society, the government, insurance companies and employers are to blame for letting these dangerous multiple pregnancies occur.

My first day of fellowship training in Reproductive Endocrinology at the Jones Institute was the day the Institute moved from the old quarters at the medical school to their new location at Hoffheimer Hall.  Movers carried boxes laden heavy with text books and the physician giants of IVF I had up until now only read about were picking up odds and ends from their recently departed offices.  Howard and Georgeanna Jones looked to me on that auspicious day like someone’s old grandparents rather than the father and mother of IVF.  Dr. Georgeanna, as she liked to be called, reminded me of my own grandmother.  I feared that I had come too late, that they were way past their prime and I would not be able to learn from them.  It was after all 1985 and they had been leaders in infertility since the 1960’s.  Dr. Howard was let go from Johns Hopkins Hospital almost 7 years earlier for reaching the retirement age.

They had planned to settle on the Maryland shore and spend time on their second love after fertility, sailing.  Instead, an old friend of theirs from Johns Hopkins from the 1960’s, Mason Andrews, helped found a new medical school in Norfolk, Virginia and now wanted their help to build the division of reproductive endocrinology, infertility (REI).  Eastern Virginia Medical which later changed its name to the Medical College of Hampton Roads was new and barely known by anyone outside of Virginia at that time.  Mason, a southern gentleman in his 60’s, soft spoken with a sharp wit and former Mayor of Norfolk, was successful in talking them into spending a few more years teaching so they bought a cozy house on the Elizabeth River 10 minutes from the school.

The Joneses hadn’t finished unpacking when the greatest fertility event of all time hit the news.  Patrick Steptoe and Robert Edwards had succeeded in Great Britain with creating a new life through a process known as In Vitro Fertilization.  The Joneses had worked with Professor Edwards years ago and were themselves well known in the field so it was natural that journalists came to their home to interview the erudite couple.  Dr. Howard talked about the genius of Professor Edwards and how he was not surprised that he achieved success.  Almost as an afterthought at the end of the interview, Dr. Jones was asked if IVF could be performed successfully in Norfolk.  In Dr. Howard’s pinpoint precision fashion and with his classic radio announcer voice, proclaimed that they certainly could develop IVF and with sufficient funds they could even create a successful program in Norfolk.  I have seen videotapes of Dr. Howard talking about this moment and it conjures up images of Babe Ruth promising to hit a homerun for the sick boy in the hospital then pointing to the fence just prior to him knocking one out of the park.

Well, the Joneses hit the homerun as predicted and by the time I arrived in 1985, Norfolk was the center of the IVF universe. Experts worldwide travelled to Norfolk to train and to teach.  Prior to the Joneses entering the playing field of IVF, the world averaged one baby a year from IVF.  Dr. Georgeanna introduced the concept of stimulating a woman’s ovaries with gonadotropin hormones in order to produce multiple eggs, thereby increasing the odds of retrieving healthy mature eggs, getting them fertilized and creating embryos that had good pregnancy potential.  Patients travelled from all over to have their IVF at Norfolk where the success rate, in 1985, was a world leading 15%.

I was excited beyond belief that this was my world now.  I arrived early that first day of my fellowship dressed in a brand new shirt and tie eager to learn and impress.  I managed to be accepted to this most competitive fellowship in part because I had been reading reproductive endocrinology for over 5 years.  I went through my ob gyn residency with the intention of specializing in REI and IVF.  In 1980 I began my training in REI mentored by Zev Rosenwaks, who convinced me that I could not possibly learn as much in any other residency as I would with him in Stony Brook.  So, I joined Zev, who had trained with the Joneses at Johns Hopkins, and he helped me start a residency clinic in REI at StonyBrook where I trained until 1985. Those five years I had been preparing for this moment in July 1985, to do my fellowship with Howard and Georgeanna Jones at the world famous Jones Institute in Norfolk, Virginia.

That first day, during office hours, I was following Dr, Georgeanna who was seeing her private patients.  Training begins.  She asked, do I know about the two cell theory to the luteal phase? I was dumbfounded.  I  had never come across such a concept in any of my reading.  Little did I know, Dr. Georgeanna had a knowledge base and theories in reproductive endocrinology that few others could rival.  She explained about the large cell and small cell and how the small cell is activated 10 days after ovulation by the pregnancy hormone, hcg.  In its absence the large cell dies, progesterone decreases and a woman menstruates.  In its presence the activated small cells continue to pump out progesterone and support the pregnancy.  How exciting! I realized that I would spend every possible free moment talking reproductive endocrinology with Dr. Georgeanna. She knew all the REI secrets.  She was the endocrinologist expert of the team.  She was also the heart of Norfolk.  She empathized with her patients and would go out of her way for them to help her patients achieve their dream, and that dream was to build their family.  Dr. Howard was the surgeon, the geneticist and the spokesman in addition to being the leader.  He was able to motivate and direct like a general leading his troops to battle.  Everyone on his team was critical in his view to their ultimate success.  He loved to say, “a chain is only as strong as its weakest link”.  He did what he could to ensure the integrity of each link.

Despite his age which was into his 70’s, Howard exercised regularly, was in excellent shape and in my mind was the original Macho Man.  I remember observing him operate, not always delicate, but experienced in fertility surgery like few others.  He was never intimidated and if the job called for raw muscle he was eager and willing to provide it himself.

I completed my two year fellowship in 1987, having learned an enormous amount of information and prepared to start my own IVF program.  However, the Joneses asked me to stay on as an assistant professor, to help start an embryo cryopreservation program and direct the donor egg program.  How could I refuse such an opportunity? I saw patients next door to Dr. Georgeanna and around the corner from Dr. Howard. Zev Rosenwaks was down the hall.  I could present every patient to whomever I thought would know the most about my patient’s problems.  This became an even better learning experience than my fellowship.  There were four of us in the IVF rotation, Zev Rosenwaks, myself, Suheil Muasher, a fellow who was two years ahead of me in training and Anibal Acosta, the Howard Jones of Argentina.  Rosenwaks and Acosta were often lecturing so Suheil and I performed more of the IVF that year. It was an exciting time.  We started doing retrievals transvaginally instead of laparoscopically.  We were experimenting with lupron and pregnancy rates were exceeding 25%.  I was doing my life’s dream working in IVF, helping women in need of help with conception achieve their dream of making their family.

Times were changing. Successful IVF programs were springing up throughout the nation.  It was the spring of 1988 when I returned home and started the first successful IVF program on Long Island dedicated to Howard and Georgeanna Jones who through their time, efforts and knowledge trained me and in so doing passed the baton of successful family building through the miracle of IVF.  Today, we remember these giants of IVF who started it all.  Mason Andrews and Dr. Georgeanna have since passed on.  Dr. Howard, now in his 90’s and how he describes it as late in the 9th inning is still occasionally involved in trying to make IVF more accessible to the public.  They were erudite medical pioneers who are responsible for the hundreds of thousands of babies who have been born through the technology that they helped create and promote.  They were the original teachers of IVF who selflessly shared their knowledge with others so that they also may help their patients conceive.   I am eternally thankful for the opportunities and training I received there from them, from Zev Rosenwaks, Suheil Muasher and from others at the Institute.

I was at a meeting with one of the insurance companies when I was asked, “How do you educate patients regarding the risks of multiple pregnancy?” I realized that as much as I try to counsel patients and teach them that we had limited written materials and no audio visual. It was at that point that we decided to create our patient education program. First we hired an expert patient educator, Pamela Madsen, former founder and president of the American Fertility Association. With her assistance and with the help of my son Dan, we have produced a number of online tools for our patients:

We launched this blog, the fertililty doc, insights, information and musings on the world of fertility, infertility and reproductive medicine which covers everything from current news to new programs offered to informational videos and more.

We have developed a message board to assist patients in reaching out for answers to their questions. There is also a cycle buddy board that patients can utilitze to connect with and offer support to their fellow patients going through similar experiences.

The newest of our projects is an ongoing video series called Journey to the Crib: Fertility Talk with Pam and Dr. Dave which will consist of a new topic each week. We went with a casual format that actually takes place in the living room of my house.

Here are the first two episodes of Journey to the Crib, the first is an introduction to the series and the second one which is the topic for this week is High Order Multiple Births. I welcome you to visit our new educational sites as often as you wish. I hope they work to help educate you on fertility and increase your knowledge and awareness to help you in your own personal journeys. Please feel free to ask questions and to comment by clicking the comments button below.

• Injections of the natural hormones FSH and/or LH (gonadotropins) that are normally involved in ovulation every month are used for this purpose

• Additional medications are used to prevent premature ovulation

• An overly vigorous ovarian response can occur, or conversely an inadequate response

Medications may include the following (not a complete list):

- Gonadotropins, or injectable “fertility drugs” (Follistim®, Gonal-F®, Bravelle®, Menopur®): These natural hormones stimulate the ovary in hopes of inducing the simultaneous growth of several oocytes (eggs) over the span of 8 or more days. All injectable fertility drugs have FSH (follicle stimulating hormone), a hormone that will stimulate the growth of your ovarian follicles (which contain the eggs). Some of them also contain LH (luteinizing hormone) or LH like activity. LH is a hormone that may work with FSH to increase the production of estrogen and growth of the follicles. Luveris®, recombinant LH, can also be given as a separate injection in addition to FSH or alternatively, low-dose hCG can be used. These medications are given by subcutaneous or intramuscular injection. Proper dosage of these drugs and the timing of egg recovery require monitoring of the ovarian response, usually by way of blood tests and ultrasound examinations during the ovarian stimulation.

As with all injectable medications, bruising, redness, swelling, or discomfort can occur at the injection site. Rarely, there can be there an allergic reaction to these drugs. The intent of giving these medications is to mature multiple follicles, and many women experience some bloating and minor discomfort as the follicles grow and the ovaries become temporarily enlarged. Up to 2.0 % of women will develop Ovarian Hyperstimulation Syndrome (OHSS) [see full discussion of OHSS in the Risks to Women section which follows]. Other risks and side effects of gonadotropins include, but are not limited to, fatigue, headaches, weight gain, mood swings, nausea, and clots in blood vessels.

Even with pre-treatment attempts to assess response, and even more so with abnormal pre-treatment evaluations of ovarian reserve, the stimulation may result in very few follicles developing, the end result may be few or no eggs obtained at egg retrieval or even cancellation of the treatment cycle prior to egg retrieval. Some research suggested that the risk of ovarian tumors may increase in women who take any fertility drugs over a long period of time. These studies had significant flaws which limited the strength of the conclusions. More recent studies have not confirmed this risk. A major risk factor for ovarian cancer is infertility per se, suggesting that early reports may have falsely attributed the risk resulting from infertility to the use of medications to overcome it. In these studies, conception lowered the risk of ovarian tumors to that of fertile women.

- GnRH-agonists (Leuprolide acetate) (Lupron®): This medication is taken by injection. There are two forms of the medication: A short acting medication requiring daily injections and a long-acting preparation lasting for 1-3 months. The primary role of this medication is to prevent a premature LH surge, which could result in the release of eggs before they are ready to be retrieved. Since GnRH-agonists initially cause a release of FSH and LH from the pituitary, they can also be used to start the growth of the follicles or initiate the final stages of egg maturation. Though leuprolide acetate is an FDA (Federal Drug Administration) approved medication, it has not been approved for use in IVF, although it has routinely been used in this way for more than 20 years. Potential side effects usually experienced with long-term use include but are not limited to hot flashes, vaginal dryness, bone loss, nausea, vomiting, skin reactions at the injection site, fluid retention, muscle aches, headaches, and depression. No long term or serious side effects are known. Since GnRH-a are oftentimes administered after ovulation, it is possible that they will be taken early in pregnancy. The safest course of action is to use a barrier method of contraception (condoms) the month you will be starting the GnRH-a. GnRH-a have not been associated with any fetal malformations however you should discontinue use of the GnRH-a as soon as pregnancy is confirmed.

- GnRH-antagonists (Ganirelix Acetate or Cetrorelix Acetate) (Antagon®, Cetrotide®):

These are another class of medications used to prevent premature ovulation. They tend to be used for short periods of time in the late stages of ovarian stimulation. The potential side effects include, but are not limited to, abdominal pain, headaches, skin reaction at the injection site, and nausea.

- Human chorionic gonadotropin (hCG) (Profasi®, Novarel®, Pregnyl®, Ovidrel®): hCG is a natural hormone used in IVF to induce the eggs to become mature and fertilizable. The timing of this medication is critical to retrieve mature eggs. Potential side effects include, but are not limited to breast tenderness, bloating, and pelvic discomfort.

- Progesterone, and in some cases, estradiol: Progesterone and estradiol are hormones normally produced by the ovaries after ovulation. After egg retrieval in some women, the ovaries will not produce adequate amounts of these hormones for long enough to fully support a pregnancy. Accordingly, supplemental progesterone, and in some cases estradiol, are given to ensure adequate hormonal support of the uterine lining. Progesterone is usually given by injection or by the vaginal route (Endometrin®, Crinone®, Prochieve®, Prometrium®, or pharmacist-compounded suppositories) after egg retrieval. Progesterone is often continued for some weeks after a pregnancy has been confirmed. Progesterone has not been associated with an increase in fetal abnormalities.

Side effects of progesterone include depression, sleepiness, allergic reaction and if given by intra-muscular injection includes the additional risk of infection or pain at the application site. Estradiol, if given, can be by oral, trans-dermal, intramuscular, or vaginal administration. Side effects of estradiol include nausea, irritation at the injection site if given by the trans-dermal route and the risk of blood clots or stroke.

- Oral contraceptive pills: Many treatment protocols include oral contraceptive pills to be taken for 2 to 4 weeks before gonadotropin injections are started in order to suppresshormone production or to schedule a cycle. Side effects include unscheduled bleeding, headache, breast tenderness, nausea, swelling and the risk of blood clots or stroke.

- Other medications: Antibiotics may be given for a short time during the treatment cycle to reduce the risk of infection associated with egg retrieval or embryo transfer. Antibiotic use may be associated with causing a yeast infection, nausea, vomiting, diarrhea, rashes, sensitivity to the sun, and allergic reactions. Anti-anxiety medications or muscle relaxants may be recommended prior to the embryo transfer; the most common side effect is drowsiness. Other medications such as steroids, heparin, low molecular weight heparin or aspirin may also be included in the treatment protocol.