We never planned nor expected to have twins, but we feel exceptionally fortunate to have the best of both worlds: a boy and a girl. It was a great hand of luck, which, minus the infertility part, has been our story from the beginning of this journey.

We knew we wanted kiddos, but like many couples wanting kids nowadays, we thought we had a good reason to postpone starting a family. Our plans were to travel the world, come back home and then grow kids. We sold everything we owned, bought two motorcycles and traveled across 30 countries over the span of three years before returning to San Francisco. Only later did we discover that infertility would be our issue.

We tried to conceive on our own for a year without luck. When we decided to get preliminary blood work to help solve our mystery, each test came back normal. Our prognosis wasn’t good: unexplained infertility.

I spent the next three weeks researching our fertility options online—looking at doctors and clinics, and comparing their success rates and patient reviews. During my research process, I learned how quickly the chances of having a family were dwindling for a couple of our age. A 40 year old healthy woman has around a 25% chance of a live birth through IVF. While a woman over 42 years of age, has a 5% or less chance of conceiving. I was almost 41 years old.

I felt very good about Pacific Fertility Center as all five of the doctors were researchers in the field of fertility with exceptional resumes. Furthermore, as practitioners, they seemed more experienced than most, in working with women past age 40. I chose the first doctor I spoke with, Doctor Ryan, based on her online profile. She was straightforward, and took the time to explain our treatment to us both verbally and visually (drawing out diagrams). She has a rare ability to conduct a professional yet personal relationship. She is genuinely warm, personable, and interested in her patients. Pierre and I knew after one meeting that we wanted to work with her.

The injections and the medications became a kind of ritual for us. The experience brought Pierre and I closer. Of the seven eggs collected, four developed into embryos. On the third day, all four were transferred and we started to wait, hopeful it would “work”. Six weeks later, late in the evening, I began to bleed and was sure I had miscarried. For the first time I realized what it meant to me to have a child. I wouldn’t let myself believe I had miscarried, but I also recognized the emotional tail-spin I’d go into if I had in fact lost the pregnancy. We both must have had the saddest night of our lives. Early the next morning, I went in for an emergency appointment. The image came up on the ultrasound screen and, within seconds, the doctor turned to me and exclaimed: “You have twins!” Pierre and I looked at each other elated. Twins! It was the best fortune imaginable.

Max and Emmanuelle are now 9 months old. We barely remember life before them. They are healthy, incredibly good-natured babies. Pacific Fertility Center was the best choice for us, but not entirely based on our (and Dr Ryan’s!) success. We knew it was a one-shot deal and the result, a girl and a boy, could not have been better.

For parents thinking about using IVF, I would recommend setting a limit in the number of attempts before you begin treatment. Knowing we were with the best doctors allowed us to approach the procedure in a more relaxed way. Knowing our odds, however, we did feel like this was our last hope. Now we find it more amusing and gratifying to find ourselves looking for our own characteristics in our kids. We see Max and Emmanuelle as little individuals who have been placed into our care, two beautiful and unique little people whose personas are going to blossom in front of our eyes.

We are incredibly grateful to Dr. Ryan and the team at PFC for allowing us to know the joy of giving birth. However, we are most grateful to be parents. Above all else, it is this unconditional love that lasts 18 years and beyond, that really defines parenthood. Even if your fertility issue doesn’t permit the use of your own genes, know that you still will be a very loving, loved and fulfilled parent.

–Submitted by Merritt Grooms

The article in January’s issue of Fertility Flash, Conception at 40 and Beyond – Does IVF Help? contained some errors in the table. The following is a reprint of the article with corrections.

We all know that fertility declines with female age but what is not certain is how much does in vitro fertilization improve one’s chances of conception if a woman/couple is having problems conceiving on their own?

The table below is one I often use when counseling patients 40 and over about their chances of conception with in vitro fertilization.

This table represents pregnancy outcomes with PFC patients from January 2003 to March 2008, so most of the viable pregnancies tabulated here have been delivered.

One thing to note is that over half of the patients that get a positive beta-hCG result do not end up delivering a baby. This is consistent with the observation that most embryos from women 40 and over have abnormal numbers of chromosomes.

Another thing to note is that pregnancies after age 43 are exceedingly rare, even with IVF. We encourage most women over age 43 to strongly consider ovum donation.

World-wide, over half the babies born from assisted reproduction to women over age 40 are born from ovum donation, not from their own eggs.

In southern California last month, a set of octuplets were born via Cesarean section. The mother, Ms. Nadya Suleman, recently divulged that this pregnancy resulted after undergoing in vitro fertilization (IVF) treatment. Most previous cases of high-order multiple births have occurred after treatment with injectable fertility drugs combined with intrauterine insemination (IUI). This case is unusual in that the treatment was IVF, where the number of embryos transferred back to the patient is a conscious decision on the part the patient and her physician. We are reassured to hear that Ms. Suleman and the octuplets are thus far doing well, but certainly the potential complications of premature birth may not present themselves until much later in each of these octuplets’ coming days, months, or even years.

We are very concerned that such an event of a high-order multiple pregnancy has occurred, and would like to reiterate that PFC takes the issue of multiple gestation very seriously. PFC has been taking steps to minimize the risk of multiple pregnancy for several years. Balancing high pregnancy rates with low pregnancy risk improves pregnancy outcomes. Achieving that balance and reducing the risk of multiple pregnancy is our goal. In all treatment cycles that we perform here at PFC, our ultimate aim, and any recommendations we provide, are with the hope of achieving a singleton pregnancy- the safest pregnancy.

Fertility physicians are very aware that one of the most important side effects of fertility treatment is multiple gestation. Our governing organization, the American Society of Reproductive Medicine (ASRM), as well as the Society for Assisted Reproductive Technology (SART) have worked steadily to formulate evidence-based guidelines for the number of embryos to be transferred in assisted reproductive technology (ART) cycles. These guidelines were first established in 1996 and were updated in 2006 to reflect improved success rates with ART. Over the past decade we have seen a significant decrease in the number of high-order multiples in the US.

We at PFC adhere to the ASRM and SART guidelines. These guidelines provide the flexibility to give each patient treatment individualized to her needs, and her best chance to become pregnant; while minimizing the risks of a high-order multiple pregnancy.

SART member clinics are committed to following these guidelines, although it would appear that the guidelines were not followed in Ms. Suleman’s case.

Pacific Fertility Center is pleased to share our delivered pregnancy rates for 2007 and our preliminary clinical pregnancy rates for 2008. These outstanding pregnancy rates are made possible thanks to our team of board certified Reproductive Endocrinology and Infertility specialists, as well as, our highly trained embryologists.

Clinical pregnancy reflects the finding of a pregnancy sac in the uterus following transfer. Delivered pregnancy rate will be lower after accounting for miscarriage and pregnancy loss, particularly in older age groups.

Pacific Fertility Center Preliminary Clinical Pregnancy Rates for 2008

Delivered Pregnancy Rates 2007 (as reported to SART and CDC)

We all know that fertility declines with female age, but what is not certain is how much in vitro fertilization (IVF) improves one’s chances of conception if a couple/woman is having problems conceiving on her own.

The table below is one I often use when counseling patients 40 and over about their chances of conception with in vitro fertilization.

This table represents pregnancy outcomes with PFC patients from January 2003 to March 2008, so most of the viable pregnancies tabulated here have been delivered.

One thing to note is that over half of the patients that get a positive beta-hCG result do not end up delivering a baby. This is consistent with the observation that most embryos from women 40 and over have abnormal numbers of chromosomes.

Another thing to be aware of is that pregnancies after age 43 are exceedingly rare, even with IVF. We encourage most women over age 43 to strongly consider ovum donation.
World-wide, over half the babies born from assisted reproduction to women over age 40 are born from ovum donation, not from their own eggs.

This past summer, Dr. Herbert and I had the opportunity to travel to Barcelona, Spain for the annual meeting of the European Society for Human Reproduction and Embryology (ESHRE). Though largely attended by Europeans, this scientific meeting draws physicians, embryologists and scientists from around the world to discuss their research, attend courses and lectures, and discuss the latest topics in our field.

Here are some of what I consider the highlights of the meeting:

Outcome of 1267 Children after Frozen Embryo Transfer – Study from Denmark

Control group: Fresh IVF pregnancies

Only 14% were twins

They compared 957 frozen embryo singletons with about 10,000 fresh IVF singletons

No increase in neurological problems or malignant diseases on FET babies.

No differences were seen when IVF or ICSI-derived frozen embryos were compared.

Results similar to prior Swedish study showing better outcomes for FET babies.

Why a better outcome? The authors postulated that patients conceiving with FET were more likely to be good prognosis patients.

Three years of clinical application in human oocyte vitrification (freezing): high survival rate and healthy deliveries (from Rome)

3138 unfertilized eggs were frozen between 10/04 – 10/07.

They reported on 295 cycles with planned embryo transfer – all patients were less than 40 years old. The patients underwent programmed endometrial preparation using a GnRH agonist (like Lupron) and oral estrogen and vaginal progesterone.

770 unfertilized eggs were thawed, 98.9% survived the thaw. The eggs were injected with sperm 2 hours after thawing and the embryos were transferred on Day 3.

Results: Avg. # embryos transferred = 2.3

Clinical pregnancy rate = 27.8%

Implantation rate = 13% per embryo, 11.3% per thawed egg. That is, about 11% of the eggs thawed resulted in a viable gestation.

58 deliveries of 63 babies, mean birth weight = 2930 grams

They experienced no congenital malformations at birth.

Then, the most controversial paper presented by Dr. Norbert Gleicher, an RE from New York.

The title: “In contrast to prevalent opinion, twin pregnancies after fertility treatments are medically, ethically and economically desirable outcomes.”

His arguments to support this opinion:

Most couples want to have more than one child. Therefore, they will need to undergo two pregnancies of two separate singletons vs. one pregnancy of twins to have two children. He argued that twins born after ART have much better pregnancy outcomes (by 30-50%) than spontaneously-conceived twins. He also argued that the accumulated costs and risks to mother and babies are higher with two singleton than one twin pregnancy.

Despite these intriguing arguments, this paper was hotly debated and essentially disavowed by the European ART community. Europe has led the way in legislating for avoidance of twins. In fact, in Denmark, if a woman has twins after the transfer of more than one embryo using IVF, she incurs any neonatal costs out of pocket.

Corifollitropin: a modification of Follistim to make it a once-a-week injection.

As most people know, the medication we most commonly use for fertility treatment, Follistim, is pure human FSH, manufactured using recombinant DNA technology. The company that makes Follistim, Schering Plough, is working towards FDA approval of a modified version of Follistim, called Corifollitropin, that will make the drug very long-acting. It may be possible to only take one injection per week!

A symposium at ESHRE presented information from studies underway in Europe and USA. Corifollitropin is not in clinical use yet, even in Europe, but will be very soon.

For those of you interested in the details, Corifollitropin is the recombinant FSH molecule + 22 C-terminal peptides from beta-hCG, It does not bind to the LH receptor.

This modification lengthens the half-life of Follistim from 22-34 hours to 60-74 hrs for Corifollitropin. After injection peak levels are reached in 2 days then slowly levels decline. The recommended regimen will be one dose per week, starting at baseline, switch to daily recombinant FSH after that.

	Carolyn Givens, M.D. was the first in San Francisco to successfully initiate a pregnancy using intracytoplasmic sperm injection (ICSI). She currently co-directs the Bay Area Pre-Implantation Genetic Diagnosis Program (PGD) and is director of PFC’s PGD program.
	Carl Herbert, M.D. was instrumental in the development of one of the first assisted reproductive technology programs in the United States and has been performing IVF longer than any physician in the Bay Area.

Question: A friend of mine recently conceived a couple of months after two failed IVF cycles. Did she really need IVF in the first place or did the IVF change things to make it more likely she would get pregnant on her own later?

Answer: For some couples, IVF is necessary because the woman’s tubes are blocked or because the sperm count is drastically low. For these patients, IVF is probably the only way they are going to conceive. For the rest of our patients, those with endometriosis, mild male factor, decreased ovarian reserve, age-related, or unexplained infertility, there is some chance of conception, however low it is. For these patients, IVF is a way to boost (often dramatically) the chances of conceiving sooner than later.

For example, for a couple that has unexplained infertility of one to two years’ duration, the statistical chances that they are going to conceive on their own are probably in the range of 3% per month. Depending on the woman’s age, IVF could increase that to 20-50% per month of treatment. But even if she doesn’t happen to get pregnant with IVF, and the couple continues to try on their own, their chance of conception returns to that 3% per month, so they may conceive, even after a failed IVF attempt. There is no reason that the IVF itself should make that couple more likely to conceive later.

An Example X-Ray of a normal HSG	An example X-Ray of an abnormal HSG

Infertility due to blocked fallopian tubes was a common cause of infertility in the 1970’s and 1980’s. Some textbooks from that era quote an incidence as high as 25% of all infertility causes. At Pacific Fertility Center in 2005, only 10% of our in vitro fertilization patients were noted to have a tubal factor contributing to their infertility. Fallopian tube damage is most commonly due to prior infection with a sexually transmitted disease such as gonorrhea or Chlamydia. Most chlamydial pelvic infections are relatively asymptomatic and may go unrecognized; therefore many patients with tubal obstruction are unaware they have a tubal problem. Better safe-sex practices and improved screening of young women are possible factors for the lower incidence of tubal disease we are seeing, at least in our Bay Area infertility population.

Even though there is less tubal factor infertility these days, if there is a tubal obstruction, the course of fertility treatment becomes quite definitive: in vitro fertilization. No other treatments, including surgery, are likely to result in a healthy intra-uterine pregnancy. Therefore, we are still advocating some type of screening test for tubal factor in the evaluation of infertile couples.

There are two common ways to determine whether there is tubal obstruction. One is surgery, where dye is passed through the cervix, uterus and tubes, and there is direct visualization of the flow of the dye out the ends of the tubes into the pelvis. The other is the HSG, or hysterosalpingogram. The HSG is an X-ray procedure that involves placing into the cervix a small flexible catheter with a balloon around the tip to hold the catheter in place and close off the cervical opening. Radiographic contrast dye is then instilled into the uterine cavity, using a syringe attached to the tube. Under X-ray visualization, the dye is tracked into the uterine cavity and into the tubes. Pictures are taken during this process to document the shape of the uterine cavity and whether or not the dye enters and flows through both tubes into the pelvis.

HSG procedures are usually performed by radiologists; however, if there is difficulty placing the catheter securely into the cervix, the radiologist may ask the patient’s gynecologist to assist. This test is valuable in determining tubal blockages, but it has some disadvantages. It is very important to get the balloon properly inflated in the cervix to keep enough pressure on the fluid (no back flow into the vagina) so it will enter the fallopian tubes. Unfortunately, this pressure on the walls of the uterus can cause the uterus to contract, causing the patient to experience significant cramping. For this reason, it is recommended the patient take 2 or 3 ibuprofen prior to the procedure.

In some cases, the pressure is enough to cause the smooth muscle walls of the fallopian tubes themselves to spasm, blocking any dye from entering the tube. Sometimes the dye flows so easily through one tube that there is not enough pressure generated to get the dye to fill the other tube. These are some of the drawbacks of the procedure. This is why, even when we get a report of one-sided tubal obstruction, we are often skeptical that this is really due to some abnormality of the tube.

Although there are some false positives associated with this test, if the dye fills both tubes and does not flow out the ends of the tubes, this is highly suggestive of true tubal obstruction. In this instance, IVF is indicated.

At Pacific Fertility Center we aim to help our patients build a healthy family. To build healthy families, maximum pregnancy rates are a goal, but maximum pregnancy rates must be balanced by consideration of risk, the chance of an adverse outcome. High pregnancy rates with minimal risk is PFC’s goal.

The risk of multiple pregnancy has increased as fertility therapy has improved. The wider use of gonadotropins in the 1990s to induce ovulation of multiple follicles, as well as the use of more effective laboratory and clinical IVF methods, resulted in production of more and healthier oocytes and more embryos, and increased the chances of multiple pregnancy. The very dramatic improvement in success rates over this time period resulted in many more children being delivered after fertility therapies, but also more twins, triplets, and higher order multiples.

Over the last twenty years, the incidence of multiple birth has increased nationally. According to the National Vital Statistics Report and the March of Dimes, the incidence of twins has increased by two-thirds, and the number of triplets and quadruplets has increased four-fold since 1980.

It is thought that about one-third of multiple pregnancies arise because women are waiting until later in life to conceive; age is a well-known risk factor for multiples. Another third arise from use of ovulation induction with gonadotropins (Pergonal, Follistim, Gonal-F, Repronex) alone. Less than one fifth of multiples are from assisted reproduction techniques (IVF and related procedures). Assisted reproduction in 2003 accounted for 18% of multiple pregnancies, 16% of twins and 44% of triplets ¹.

The risks to the children of multiple pregnancy are numerous. Low birth weight and very low birth weight are increased in children born as multiples. The chance of low birth weight (<2500g) is increased 8 times in twins. Cerebral palsy is increased 4 times, neonatal death risk by 7 times ^{2, 3}.

The risk to the mother from multiple pregnancy is also increased. Pre-eclampsia, high blood pressure, preterm labor, and premature rupture of membranes are all more common with multiple pregnancy ⁴ .

Multiple pregnancy is also expensive. It is estimated that twins alone cost the healthcare system some $600,000,000. There is clear evidence of an increase in parenting stress and divorce in families of multiples ^{5, 6} .

The need to assure our patients of the highest quality care requires that we bear this in mind – the healthiest pregnancy is a singleton pregnancy.

Pregnancy requires the cooperation of sperm and egg, accurate transcription of the early genetic code in the developing embryo, a fertile spot for attachment to the mother in the uterus, and a route for getting there. All other factors being equal, pregnancy rates almost double when two embryos are transferred instead of one, and increase again when a third and fourth embryo are added. The desire for high pregnancy rates has driven a desire for more embryos to be transferred ⁷ .

Improvements in insemination technique, embryo culture methods, and transfer efficiency have added substantially to pregnancy rates. Each embryo transferred today has a considerably higher chance of producing a pregnancy than an embryo transferred twenty years ago. Such improvements have enabled us to think about ways to reduce the risk of multiple pregnancy by transferring fewer embryos.

The development of blastocyst (day 5 embryo) culture techniques allows the selection of high quality embryos for transfer. The blastocyst stage requires advanced incubation techniques with low oxygen incubators and specialized culture media. A tight quality control system is also required. The blastocyst stage is a more advanced stage in which the genetic code of the embryo is fully activated and working. Only the healthiest of embryos can move to the more advanced stages, allowing selection of the best embryos for transfer.

In 2006 the ASRM published guidelines for number of embryos to transfer:

These guidelines encourage all of us to transfer ‘just enough’ embryos to achieve pregnancy.

Pacific Fertility Center has pioneered techniques of transferring fewer embryos. Last year, in 2007, our program of single embryo transfer in oocyte donation recipients produced a 66% pregnancy rate. The multiple pregnancy rate in this group was minimal. Utilizing a single embryo, two-thirds of patients were able to conceive a singleton pregnancy. This pregnancy rate was very similar to the overall pregnancy rates regardless of the number of embryos transferred.

Today half of our patients using oocyte donation elect to transfer a single embryo. Single embryo transfer is not always possible. Our criteria include age and embryo quality. A young woman (under age 35) with high quality blastocyst stage embryos and a healthy uterus can reliably transfer a single embryo and achieve high pregnancy rates. An older woman (over 40) may need to transfer 3 or more embryos to achieve a good pregnancy rate. Because of the higher number of embryos transferred, the risk of multiple pregnancy remains higher in these older age groups⁹ .

Pacific Fertility Center is very pleased to offer these techniques of single embryo transfer as some of the best and most advanced fertility treatment technology available. We are moving closer to our goal of growing families, one healthy baby at a time.   Philip Chenette, MD

1. Martin, Births: Final Data for 2003. National Vital Statistics Reports, volume 54, number 2, 2005
2. Scher, Ped Res, Vol. 52:671-81, 2002
3. Rutter, J Child Psychol Psych, Vol. 44:326-41, 2003
4. Pinborg, Human Reproduction, Vol. 18:1234-43, 2003
5. Griesinger, Hum Reproduction, Vol. 19:1239-1241, 2004
6. Glazebrook, Fertil Steril, Vol. 81:505-11, 2004
7. Paulson RJ, Fertil Steril., Vol. 53:870-874 , 1990
8. Fertil Steril, Vol. 85, Suppl. 4, 2006
9. Pacific Fertility Center 2007 IVF Statistics

As a lesbian couple, we were aware that getting pregnant might be a challenge and might require medical intervention, but decided to try at home anyway.  Since Jean is older it made sense for her to carry first.  In 2002, we began the process of trying to conceive with our known donor.  We had a few challenges to overcome. Our donor was from out of state and we had to use a shipping kit designed by University of Chicago Andrology Lab to maintain the viability of the sperm.  We hired a midwife to come to our home, clean the semen sample and do the insemination.  In 2004, after two years of trying and many dollars spent, it became apparent that we were not going to be successful on our own.

We spoke to our OB/GYN who recommended that we work with a fertility specialist.  On a recommendation from a Pacific Fertility Center staff counselor, Peggy Orlin, we contacted Dr. Eldon Schriock at PFC.  Though the initial paperwork and set up seemed daunting, we were able to complete the required items quickly and were ready to start fertility treatment with Dr. Schriock in March 2005.  Jean was set to do the “Clomid challenge” test on our first attempt.  With new FDA regulations looming in May 2005, we felt we had limited time to get Jean pregnant with our current donor so the pressure was on.  Although the PFC staff was not initially familiar with our shipping kit, they were more than willing to work with it and help us with the logistics.  Jean had a fortunate experience with Clomid and on April 15, 2005 with 3 good follicles we completed our first IUI with PFC.  Two weeks and 3 positive pregnancy tests later, we confirmed that we were in fact going to have a baby.  It was hard to believe that after so many years and tries it was actually happening.  Now 3 years later we have a beautiful and fun two year old girl named Logan.

When Logan was 5 months old, there was an accident in my family that gave us pause.  We realized life is short and you never know what is in store for you around the next corner .We decided to begin the process of trying to get Marni pregnant. In May 2006 we made the decision that we would begin the process at home, but needless to say, we were unsuccessful. After 6 months we would again meet with Dr. Schriock and his fabulous team of nurses and doctors.    Because of our history with PFC, we were able to quickly begin the process and get started trying to achieve pregnancy at PFC.

With the new FDA regulations now in place we had a host of new hoops to jump through. Once we cleared the list of hurdles, we began our attempt to get Marni pregnant.  After many different fertility treatments (Clomid, Letrazole, and Follistim), three different PFC doctors (Dr. Schriock, Dr. Ryan and Dr. Givens) all suggested that if we were committed to our donor then we should seriously think about IVF as an option because of the quality of his frozen/thawed sperm.  In October 2007 we began the IVF process.  Though there was a lot to manage and keep track of (when to give shots, appointments, blood tests, etc.) we never felt alone.  The PFC doctors, nurses and staff were always available for a phone conference to answer any questions or concerns.  In late November 2007 we completed IVF – the egg retrieval and embryo transfer process.  Four embryos were implanted out of the seven that fertilized.  In December 2007, two weeks later, we received the positive blood test result and were ecstatic.  Unfortunately, within days of the positive pregnancy result it became clear that this was not going to be a viable pregnancy.  Marni had apparently been pregnant with twins. She miscarried the first embryo and had to undergo not only the abortion pill, but a subsequent D&C to remove the second gestational sac.  Dr. Schriock and all of the staff, nurses and other doctors were available for emotional support and medical guidance throughout the process.

We completed our second egg retrieval and awaited the fertilization results.  Our hopes were high but we were realistic and knew that anything could happen. As it turned out, Marni’s second round of IVF was unsuccessful. Though the quality of embryos was better than in the first cycle, she did not get pregnant.  We had a few conversations with Dr. Schriock and determined that if she were to continue trying to get pregnant, it would take an ovum donor and a lot of money.  We decided to have Jean try again, because we wanted to be pragmatic and realistic and keep the goal of adding to our family in mind.  Jean is currently under Dr. Schriock’s care and last week she completed a course of Clomid and an IUI.  We are now in the waiting period and are hopeful for a positive result.

Our experience with PFC, Dr. Schriock and all the other staff has been great.  We had a few bumps along the way but the doctors, nurses, office manager and staff responded quickly and effectively.  We always felt at ease to express concerns and ask questions.  Everyone we encountered at PFC has a good understanding of how emotional this process can be and has always been empathetic in their dealings with us.  We never felt uncomfortable as a lesbian couple.  We would absolutely recommend PFC for their cutting edge technology, knowledge and exceptional care during this highly emotional event.

Best Regards,
Marni & Jean