As a Florida IVF Doctor or Reproductive Endocrinologist, I agree with the new recommendations for older infertility patients.  In our Florida IVF clinic in Sarasota and Bonita Springs, I have been discussing the new recommendations for older IVF patients for quite some time.  Richard Reindollar’s team has reported in both the “Fast-track” study and in the “Fort T” studies that patients should made aware of the differential chances of pregnancy associated with different treatments.  He has demonstrated that older patients benefit from more aggressive treatment like IVF sooner rather than later.

As I discuss on a daily basis, older patients have a decreased chance of pregnancy because they make more genetically abnormal embryos.  In the past, many good Ob/Gyns and Reproductive Endocrinologists were hesitant about moving patients quickly to IVF due to the fear of multiple pregnancies and associated severe complications like pre-term birth and a much higher risk of neonatal morbidity, mortality, and congenital anomalies associated with twin and higher order pregnancies.  With current scientific advances, even older patients can be treated with single embryo transfers after pre-implantation genetic screening of blastocysts. The application of PGS for a planned single “Euploid” (and embryo with 23 pairs of chromosomes) transfer allows patients of all ages to have implantation rates with a single embryo that are higher that even implanting 3 or more embryos that have unknown genetic makeup.

Below is a recent Bulletin from the American Society of Reproductive Medicine detailing the results of these studies:

ASRM Bulletin

Volume 16, Number 25

May 6, 2014

Highlights from Fertility and Sterility

Older Women Should Move More Quickly to IVF

A new study demonstrates that, for couples of older reproductive age with unexplained infertility, immediate IVF is the most efficient treatment, resulting in fewer treatment cycles and a higher live birth rate.

In an NIH-funded, randomized clinical trial, 154 couples receiving infertility treatment at Boston IVF and Brigham and Women’s Hospital were randomly assigned to one of three groups to receive a specific type of treatment for their first two cycles.  One group was assigned to have IVF.  The other two groups were assigned to have intrauterine inseminations (IUI) with the female partner receiving either an oral medication to induce ovulation (clomiphene citrate- CC) or injectable ovulation drugs (follicle stimulating hormone-FSH).

If patients in the two insemination groups did not achieve an on-going pregnancy after two cycles, they were switched to IVF for their subsequent cycles.

The participating couples were required to have been trying to conceive for at least six months and to not have previously tried any of the treatments being used in the study.  The female partner had to be between 38 and 42 years old, with regular menstrual cycles, at least one ovary and fallopian tube, acceptable ovarian reserve, no disorders of the reproductive organs and no history of ectopic pregnancy.  The male partner had to have enough motile sperm.

After two cycles of the assigned treatment, differences were observed in pregnancy rates and live births between the groups.   Of patients who went straight to IVF, 49% became pregnant and 31% gave birth.  Of those taking oral medications and having inseminations, 22% became pregnant and 16% gave birth.  For the injectable medication/insemination group, 17% became pregnant and 14% gave birth.

All couples who had not been successful in their first two cycles of any treatment used IVF in their subsequent treatment cycles, but the couples in the immediate IVF group of the study went through 36% fewer total cycles than the couples who began their treatment in either of the ovulation drug/IUI groups.

By the end of the treatment, of all the couples in the study, 71% had conceived a clinical pregnancy and 46% delivered at least one live-born baby.  84% of all live births in the study came about as a result of IVF.  For those couples having a live birth, those who started with IVF took an average of two cycles to conceive, while those who started with ovulation drugs and IUI averaged three to four cycles. Of the 154 couples enrolled, 140 started and 115 completed treatment.

While the major finding of this study  is that immediately starting infertility treatment with IVF in older couples is the most effective treatment, it also showed that, if a couple chooses to try ovulation drugs with insemination first,  oral fertility drugs (clomiphene citrate) are as effective as injectables (FSH).

Richard Reindollar, MD, Executive Director of the American Society for Reproductive medicine (ASRM) was the study’s principal investigator when he was at Dartmouth Hitchcock Medical Center (DHMC), prior to ASRM.  He described how the study came about. “Previously, in the Fast Track and Standard Treatment (FAST-T) trial, we found that for young couples with unexplained infertility, proceeding to IVF after three cycles of clomiphene with IUI was more cost-effective than the standard approach at the time- which required them to go through several additional cycles of injectable ovulation drugs with insemination before allowing them to try IVF.  We suspected that immediate IVF without any prior cycles with IUI would be more effective in an older age group but needed to demonstrate that through a rigorous trial.”  Marlene Goldman, ScD, Professor at DHMC and first author of the paper stated, “While we recognize that not all patients might choose to start treatment with IVF, the results of this trial will give reproductively older patients with unexplained infertility the evidence they need to skip less effective treatments and start their families more quickly if they wish to do so.”

Goldman et al, A randomized clinical trial to determine optimal infertility treatment in older couples:  the Forty and Over Treatment Trial (FORT-T), Fertility and Sterility, in press.

Polycystic ovarian syndrome or PCOS is a very common cause of chronic anovulation and infertility.  Unfortunately, there has been  recent confusion among health care providers as to which patients are most likely PCOS.  The confusion has come from studies that have included patients as PCOS based on ultrasound criteria.

The hallmarks of PCOS are oligomenorrhea (infrequent menstrual cycles due to infrequent ovulation) and hyperandrogenism (the presence of physical manifestations of increased male hormone levels).  Sometimes the history and physical signs can be vague.  For that reason, clinicians and researchers have been looking for more sensitive ultrasound findings.  Unfortunately, the bar for the PCOS criteria for ultrasound findings appears to have been set too low.  This has led to over diagnosing many patients as PCOS.

In my clinic, it is common to see a patient that has been told that she has PCOS based on ultrasound criteria only while she reports regular ovulatory cycles.  This is incorrect.  The findings of this study may lead to less incorrect diagnoses.  The authors report on a higher threshold of 26 or more resting follicles per ovary in patients that also have oligomenorrhea and hyperadrogenism.

The analysis showed that a threshold of 26 follicles struck the best compromise between sensitivity (85%) and specificity (94%) when discriminating between women with PCOS and control participants.

“Using newer ultrasound technology and a reliable grid system approach to count follicles, we concluded that a substantially higher threshold of follicle counts throughout the entire ovary (FNPO)—26 versus 12 follicles—is required to distinguish among women with PCOS and healthy women from the general population.”

Reference:  “Updated ultrasound criteria for polycystic ovarian syndrome: reliable thresholds for elevated follicle population and ovarian volume”

Hum. Reprod. (2013) 28 (5):1361-1368.doi: 10.1093/humrep/det062

First published online: March 15, 2013

Julio E. Pabon, M.D., F.A.C.O.G.

Michele Gibbs of Sarasota tried to conceive a child for almost three years before deciding Mother Nature needed a nudge.

At the recommendation of her gynecologist, the 39-year-old registered nurse and paramedic in June visited Dr. Julio E. Pabon, a reproductive endocrinologist who performs in-vitro fertilization at the Fertility Center of Sarasota.

“It was about our only option to have a biological child,” Gibbs said. “The chance of my getting pregnant was about as good as a coin toss — about 50 percent.”

She learned on Sept. 26 that she was pregnant, most likely with twins. The technology and expertise that made that outcome possible didn’t come cheaply. Gibbs estimates her total out-of-pocket costs could exceed $15,000, including fertility drugs and special procedures.

“It’s a pretty expensive choice,” she said. But without it, “people would have to live out their reproductive years disappointed every month.”

The Fertility Center of Sarasota, 5664 Bee Ridge Road [The new address: 5100 Station Way, Sarasota], is one of about 350 clinics that have cropped up nationwide since the 1980s, prompted by medical and technological advances and a society in which more women are postponing starting families.

Obstetrician-gynecologists in Southwest Florida say they welcome the local fertility clinic because it provides a convenient extension of the services they render. Its presence creates a minimal overlap of services, but no turf war.

Before Pabon opened his practice in late 1997 — initially in another professional complex near Doctors Hospital — these physicians had to send patients as far as Tampa or Fort Myers for the in-vitro procedure.

“That is a very difficult thing for a patient to do, because they have to see the doctor every other day for half a month,” Pabon said.

Pabon is the only physician performing the procedure in Charlotte, Sarasota or Manatee counties. He declined to disclose his annual revenues, but said his expanding client base and the growing number of in-vitro fertilizations he performs, estimated to surpass 120 this year, have exceeded expectations, and in two years he will be able to build a free-standing clinic with adjoining apartments for out-of-town patients.

He and his wife and business manager, Verneda, initially thought it would take them up to eight years to develop the niche business.

“Our plan was to start a small practice and build it gradually,” he said.

But the location and the rarity of his specialty — he is one of about 800 board-certified reproductive endocrinologists in the country and the only one in Sarasota, Manatee and Charlotte counties — accelerated that growth.

“On average, you need about 300 people to make a living, just to produce a level of specialty,” Pabon said. “In Los Angeles, you throw a rock and you hit a reproductive endocrinologist. If you had two guys here, we would be starving.”

According to the Society for Assisted Reproductive Technology in Washington, D.C., about 15 percent of women of childbearing age nationwide have received infertility treatment.

Assisted reproductive technology has been used in the United States since 1981 to help women become pregnant, most commonly through in-vitro fertilization. The procedure involves extracting a woman’s eggs, fertilizing them in a laboratory and then transferring the resulting embryos into the uterus through the cervix.

In-vitro fertilization increasingly has been performed in clinics run by infertility specialists called reproductive endocrinologists — physicians who typically undergo two or three years of formal training in reproductive endocrinology and infertility beyond that of an obstetrician-gynecologist.

The ticking clock

Live births occurred in 31 percent of fertilizations attempted in 1997 in women younger than 35; 26 percent for those 35 to 37 years old; 17 percent for women 38 to 40 years old; and 8 percent among women older than 40.As more women delay childbearing, their age plays a major role in success rates. The likelihood of a successful response to ovarian stimulation and progression to egg retrieval drops; so does the chance of embryos being transferred successfully and, ultimately, of pregnancy. Consequently, treatments that result in live births also decrease in number.

But slowing biological clocks aren’t the only reason women fail to conceive. Other problems include obstructed or damaged fallopian tubes, endometriosis, ovulatory dysfunction and low sperm counts in their partners.

About 100,000 children have been born in the United States using this advanced technology, including 20,000 of them last year.

The cost of in-vitro fertilization ranges from about $8,000 to $10,000 per attempt, placing it out of the realm of many people, especially if repeated tries are necessary.

“Certainly access is a very important issue,” said Sean Tipton, spokesman for the American Society of Reproductive Medicine. “One of the knocks you get on the reputation of infertility is that it’s a yuppie women’s disease, because there are people who can’t afford the treatments. Low-income women just don’t even bother.”

Patients who feel financially pressured to get pregnant on their first try tend to favor more aggressive treatments that, in turn, raise the risk of multiple births.

“Emotionally you are so driven to be successful,” he said.

At the heart of the cost issue is insurance. Florida is not among the 13 states that have some sort of infertility legislation on the books.

A push is on, however, at both the federal and state levels, to require insurance companies to pay for these treatments. Tipton said two bills were introduced this year at the federal level — one for government employees, another for private sector workers. Neither got beyond committees.

Resolve, a national infertility association geared toward educating couples and helping them get treatment, also supports efforts to require insurers to cover infertility procedures in Florida.

Barbara Fronczak, vice president of the South Florida association chapter, said a bill introduced last year and this year by state Rep. Debbie Wasserman Schultz, D-Weston, likewise stalled in committees.

“Infertility is a disease and should be treated like a disease. Why do we cover Viagra and penile implants for men but not infertility treatments?” Fronczak said.

Efforts to require insurance companies to cover infertility treatments are paying off elsewhere.

Seeking fairness

The commission invited both sides to settle the matter. If they don’t, the case will head to federal court, where it has the potential to set a precedent.The Equal Employment Opportunity Commission ruled this year that a New York company had violated the Americans with Disabilities Act and the Civil Rights Act when it denied insurance coverage for an employee’s infertility treatments.

That case was partly motivated by a U.S. Supreme Court ruling in 1998 that referred to reproduction as a “major life activity” in a case involving an AIDS patient.

Dr. Karen Harris, president of the Florida Obstetric and Gynecologic Society, said the cost for equipment and expertise justifies the high charge for in-vitro fertilizations, she said.

“A tubal reversal runs from $15,000 to $20,000, about the same as two cycles of in-vitro,” she said. “So dollar for dollar, you get more value going through in-vitro than going through surgery. If you have X amount of dollars to spend, it’s the best way to take home a baby.”

Referrals from OB-GYNs, former patients and reproductive law attorneys account for about half the business at the Fertility Center of Sarasota.

The other half is generated by aggressive marketing. Pabon estimates that advertising on the Internet alone has resulted in 30 percent of his referrals in the past six months.

About 25 percent of his patients come from Sarasota and Manatee counties; up to 90 percent live in Florida. The remainder come from other states and overseas.

Sarasota gynecologist Michael Swor, who refers patients to Pabon, said there’s only slight overlap of services between reproductive specialists and obstetrician/gynecologists.

“I think there is some crossover, but generally Dr. Pabon and most fertility clinics have their hands full taking care of the most specialized forms of fertility treatment, like in-vitro fertilization,” he said. “A lot of the treatment involves frequent visits. I think his clinic provides our community a more convenient access to specific high-tech fertility treatment.”

Small clinic, big results

Pabon said he achieves his rate by monitoring the progress of patients more closely than doctors at larger clinics, where women might see several in the course of trying to get pregnant. At the Sarasota clinic, the only medical professionals are he and embryologist Rajesh Srivastava, whom he hired last year.Pabon claims a success rate of up to 60 percent, compared with the national average of 27 percent for in-vitro fertilizations.

In-vitro fertilization accounts for about 75 percent of revenues generated at the center. Pabon also treats infertility with other methods, such as artificial insemination and reconstructive surgery, which he performs at Doctors Hospital of Sarasota and Sarasota Memorial Hospital.

Pabon also runs an egg donation program that has grown to include 65 donors. The success rate using donated eggs is higher than with in-vitro fertilization. Twin births occur about 15 percent of the time among women using either method. Triplets are rarer still.

Pabon reviews detailed family histories, health screenings — and sometimes psychological and IQtests — to arrange compatible matches between egg donors and recipients. A common request is for a child that will look the same as the mother who will bear it.

The clinic receives $7,500 for that service; the donor is paid privately by the recipient couple, usually between $2,000 and $2,500.

Pabon, 38, said he chose to specialize in infertility during his second year of medical school.

“I did residency in OB-GYN just so that I could do this business,” he said. “I got to see what specialists were doing. I thought it was a fascinating window to new medicine and gene therapy.”

Gibbs calls her pregnancy, made possible by medical advances, a great blessing.

“I grieved for the process of getting pregnant on my own naturally, without intense manipulation,” she said. “It was fleeting.”