My husband and I never thought having a family would be a struggle.  His siblings and my cousins were all VERY fertile… why shouldn’t we be the same?  Little did we know, as we said our “I Do’s”, that a condition called endometriosis was wreaking havoc on my reproductive organs.

Such was its devastation, that our 1^st pregnancy was an ectopic, resulting in the rupture of one of my fallopian tubes.  Had we not gotten to surgery in time I could have died.  My husband still reels from the memory of me handing him my wedding ring as they wheeled me into surgery. 

My doctor at the time didn’t see my other symptoms, (missed menses, constipation, heavy menses) and the ectopic as a problem.  The solution therefore was to put me on Clomid.  After a year of trying, a family member recommended finding a new doctor. 

My new doctor stated that my symptoms were consistent with endometriosis but could not be certain without “going in” to make sure.  Thus began the 1^st of 8 laparoscopies (over 6 years) to “clean me up”.  I had 2 surgeries in one month. My endometriosis was so bad that I had organs being pulled together.  After the 1^st surgery my doctor had me begin the Clomid regimen. After 4 cycles of treatment she said that I would need IVF to get pregnant.  Here is where the true shock began.   

My husband and I live modest lives… I’m a Kindergarten teacher and he works in construction.  Although we lived comfortably, the cost of IVF seemed unattainable.  We discussed our options.  IVF meant no more vacations, no more upgrades to our home, and no more “let’s buy it” spending.  It also meant facing the dark reality that we may never have children.  After getting our finances in order we visited the Pacific Fertility Center in San Francisco, which our doctor had recommended.  It was a good visit and was our first step.  We made our plans to undergo IVF that summer, when I would be off from school. 

When the medications arrived we were in awe at the number of needles we had.  We were ready to begin this process… I had but one condition… since I was the receiving the injections, my husband had to give them.  I felt it only fair and would enable him to be very involved in the whole process.  He cried before giving me the first shot in my stomach.  He said he didn’t want to hurt me.  So I cupped his head in my hands and said, “If we want to have a baby, you have to give me the shot”.  He did.  I really didn’t have that many side effects.  What was more bothersome was the bruising and pain at the injection sites.  Of course as blood work and ultrasounds were done along the way, more meds were needed, bye- bye money.  Unfortunately, round 1 was unsuccessful and we discovered that I was not a top egg producer.  Of course my hubby had no problems with his soldiers… it was all me.  Ugh!  I think we had some extra embryos and did a frozen cycle right after… but to no avail.  Since we were committed to not only sticking to IVF but, also only doing it during the summers we had time not only to regroup, but save money.  Sadly, round 2 was also a dud.

For round 3 we had 3 embryos implanted.  And on 7-7-07 we discovered I was pregnant.  My husband said the date was a sign of good luck.  We were so happy and relieved.  We were finally going to expand our family.  Each month went by with no problems.  We had some stress… my work life was getting chaotic and my father was being a difficult patient recovering after heart surgery.  But my pregnancy was flawless.  On week 20 we discovered we were having a boy and by the end of the evening we had named him Lucius. 

However, one week later, while talking with some parents at school about the Halloween Parade guidelines, my water broke.  Even now I weep remembering that very moment.  The hospital sent me home to wait it out, hoping the hole would close.  However, by the third day I developed a fever and was going septic.  I had to deliver my little boy.  I begged with the doctor for a way to save my baby.  She said the waiting 4 more weeks until his lungs might be mature enough for survival was not possible since now I was also in danger.  There I was in the maternity ward waiting to deliver a dead baby. 

All I could think of was that I had failed my husband again.  In the months that followed I wished I had died with my baby.  I felt it was the only way I would feel less of a failure and the pain from my loss would be gone.  My husband would hold me and remind me that if he’d lost both of us he would be all alone.  I even offered to let him divorce me so he could find a wife that would be able to give him children.  I don’t think I’ve ever seen him as angry as when I said that.  He was willing to keep trying if I was.  And he felt that if we couldn’t have a child, then that’s just the way it would be.

So along came rounds 4 and 5, both of which failed.  The strain of infertility on our marriage was slight… but was there.  We were lucky to be able to talk it out.  What was difficult was the loss of Lucius.  There was pain there that lingered in each of us in different ways.  My husband started drinking more than usual and I found myself very resentful of others that had children/babies.  Amazingly, we made it through, pulling each other out of it.

When round 6 came along, with all we had been through, neither of us really expected it to succeed.  But amazingly we struck gold and were on our way to a family again.  However, this time we were on pins and needles.  I honestly don’t think I would have mentally survived another loss.  So we took every precaution possible, my mom even went to work with me 2-3 days a week to help out.  After the first trimester I decided that to be afraid was unfair to my unborn child.  Therefore, we started planning for this baby.  Registering and decorating.  Once we discovered we were having a girl… OMG!  Our joy could not be contained.  Every doctor visit that pronounced us healthy was fantastic.

Other than gestational diabetes, everything was great. Our little Lyra was born March 13, 2011 weighing 7lbs. 8 oz. and 20.5 in. long.  She was perfect!  We were perfect!

So after 10 years of trying, 6 years being IVF, 3 acupuncturists, body talk therapy, an ectopic pregnancy, and our Angel Baby Lucius, our family is now complete.  When I gaze into Lyra’s eyes and see her in awe of me I know she was worth all the sacrifices and tears.    

- Martina & Leandro

A statistic that we follow closely at PFC is our cumulative pregnancy rate in a given year.  This is defined as a patient’s chance of taking home a baby after one IVF cycle, but it includes the fresh embryo transfer and any frozen embryo transfers resulting from that one cycle.  These rates are shown in the table and are broken down into maternal age groups.  The numbers are calculated by looking at how many patients delivered a baby from their fresh transfer (43% of patients under age 35) and then adding in pregnancies achieved from the frozen embryos for patients that did not get pregnant in the fresh cycle (totals 64% of patients in this group).  So in this age group, 2 out of every 3 patients had a baby from just one IVF cycle.  Similarly, for patients doing a single cycle with donor oocytes, 74% had a baby.

Cumulative pregnancy rates have special importance since PFC is a national leader in reducing the number of embryos transferred at one time while still maintaining exceptionally high overall pregnancy rates.  One healthy baby at a time is the goal of fertility treatment at PFC and for every patient, a singleton pregnancy is the safest and most likely way to have a healthy baby.  At PFC we work carefully with every patient to reduce their exposure to a multiple pregnancy and all its risks for mother and baby.  And a big part of our strategy involves freezing embryos successfully so that we can use embryos conservatively and efficiently to generate more singleton pregnancies, and fewer multiples. Multiple pregnancies are a complication of IVF treatment, and we strive to avoid them. 

Patients with the highest risk for multiple pregnancy are those where maternal age is <35, doing their 1^st or 2^nd IVF cycle or those patients using donor eggs.  We encourage these individuals to transfer just a single embryo during their IVF cycle and to freeze their surplus embryos for use later.  The frozen embryo program has been so successful here at PFC that it provides very high pregnancy rates for those patients that need to use their embryos from the freezer.  It also means that we don’t have to risk transferring many embryos in the fresh IVF cycle because we have the frozen embryos as a back-up. And most patients that are doing elective single embryo transfer qualify for one of PFC’s financial plans (e.g. the refund plan) that include the cost of frozen embryo transfer cycles in the original price.

We believe that using embryos conservatively is the safest treatment.  And we don’t see big differences in pregnancy rates between patients that transferred just one embryo vs. those that transferred 2.  In fact, patients that received donor eggs and transferred 1 or 2 embryos had the same delivery rates, but those transferring 2 had a 35% twin rate.  In our efforts to reduce this twin rate, we are now transferring 1 embryo 60% of the time in the donor egg program, and 40% of the time in patients aged less than 35.

We want our patients to have healthy babies and we are working to make this possible while still maintaining high success rates.  Our goal is one healthy baby at a time.

 - Joe Conaghan, Ph.D., HCLD & Embryologist Erin Fischer

According to Resolve, Rep. John Lewis (GA) introduced a bill in the U.S. House of Representatives on November 30 that would provide eligible taxpayers a tax credit for the out-of-pocket expenses associated with infertility medical treatment. 

The “Family Act of 2011,” HR 3522, is a companion bill to S 965 which was introduced in the U.S. Senate in May 2011.  Advocates can now push for action on the two bills including bipartisan co-sponsorship, Committee hearings, and a vote in both chambers.

If you would like to support this bill, contact your U.S. Representative and ask them to co-sponsor HR 3522.  According to Resolve, you can do this by completing the following:

Contact your Representative right now.  It takes 3 minutes through RESOLVE’s Action Alert System. PLEASE review the online letter and personalize it with your story.  Personal content is far more impactful than a form letter.

To learn more about The Family Act 2011, visit the Resolve website today! 

In case you missed Dr. Carl Herbert on the Fertility Forum radio show, you can download the Podcast on iTunes or the MP3 version from the Fertility Forum website.  Hear Dr. Herbert talk about the History of ART, Genetics, Fertility Preservation, Egg Banking, and other topics in the field of Assisted Reproductive Technologies. 

We hope you enjoy!

Meet with a Registered Dietitian and:

Nutrition consultations consist of:

Not sure if you are a candidate for nutritional counseling?

Set up a time for a free 20 minute phone chat with the dietitian to find out!

Ask a member of the front desk or call 415-834-3000 for more information or to set up an appointment.

Alison Boden, MPH, Registered Dietitian

Alison received her undergraduate degree from UC Davis, followed by graduate training in nutrition and public health from the University of North Carolina at Chapel Hill. As a practitioner of integrative nutrition she takes a holistic approach to wellness, recognizing that the foundation for optimal health and healing begins with a health promoting diet. Her emphasis is on using medical nutrition interventions to create a basis for health promotion and healing.

A lover of good food, Alison believes that a healthful diet should be thoughtful, enjoyable and satisfying. Each meal does not only provide calories, but is an opportunity to supply our organs with the nutrients and building blocks needed for health. When the body is out of balance, as in the case of infertility, proper food choices can correct deficiencies and bring balance back to the system. What you eliminate from your diet is often as important as what you include. Consultations with Alison will help you address the key components of your diet that may be affecting your fertility and wellbeing, as well as help prepare your body for pregnancy.

Alison has experience assessing and counseling clients related to pregnancy and fertility, weight management, lipid control, food allergies, digestive health, sports nutrition, and chronic diseases such as cardiovascular, kidney disease and cancer. She views each person as a unique individual, and is dedicated to educating patients on natural ways to achieve optimal health and allowing them to take an active role in their health care decisions.

Alison is a member of the American Dietetic Association and the Women’s Health and Integrative and Functional Medicine practice groups.

Tune in and listen to PFC’s Dr. Carl Herbert talk about the History of ART, Genetics and ART, Fertility Preservation and Egg Banking on The Fertility Forum radio show Monday, October 17^th from 6-7 pm PST.

To listen, you can call in live to 877-864-4869 or go to The Fertility Forum webpage and listen there.  You can also click the LIVE CHAT button on the website to IM live during the show!

If you can’t tune in on Monday, you can download the audio AFTER the show from either the site above OR iTunes.

Don’t miss it!

Andy and I married in June of 2008.  I was just turning 39 and we tried to conceive a child “the old fashioned way” for a year  before working with PFC. We didn’t expect it to be so difficult as all signs indicated that we would get pregnant.  Andy’s sperm was normal and my FSH was good.  When we moved to the IUI and IVF processes, I responded well to the drugs, produced lots of follicles and eggs, we had nice looking embryos, and we were able to do day 5 transfers.  The doctors seemed confident.  But over the course of about 15 months we experienced 2 rounds of IUI, 4 rounds of IVF, and 2 miscarriages. 

Now it is December 2010 and we’re nearing the end of a blissfully uneventful pregnancy.  Our baby boy is due to arrive on New Year’s Eve!  It looks like our story will have a happy ending, but I don’t need to tell you how difficult the journey has been.  Instead, I’m going to try to share a little bit about how we got through it all, in the hopes that it might give you some ideas or a new perspective for your own experience.

First, Andy and I knew we wanted to be parents. We absolutely knew it would happen for us, one way or another.  Although our first preference was to have “our own” child, it was only a preference.  We both knew that if IVF did not work out for us with my own eggs, we would go the route of an egg donor.  If necessary, we knew we would move to adoption.  Starting a family was our priority and our dream.  We believed that whatever baby came into our lives, that baby would undoubtedly be the baby we were meant to parent, and we would love our baby no matter what.  Have you ever heard the Buddhist saying, “Don’t be attached to any particular outcome”?  It became one of our mantras and allowed us to stay focused on the big picture plan, as opposed to the various routes or paths that might be part of that overall plan.

Teamwork was another essential element of our journey.  I’m lucky because Andy is very detail-oriented, patient, and he was completely on board with the program.  I’m more emotional. I have a short attention span, I like information in summary format, and I can manage a calendar like nobody’s business.  We make a great team because I could endure the shots and stay on top of all those doctor appointments, but keeping track of the drugs, the dosages, the ordering—that was all Andy.  At first, I worried that we would run out of a drug that we’d need, and we wouldn’t realize it until it was too late.  However, thinking like that made me nuts.  Soon we developed a system where Andy managed all the prescriptions and ordering, he prepped my needles with the right dosages, and he tracked what we were supposed to do each day.  I did my own injections and dealt with the side effects.  Those were our roles.  I didn’t want to have to think about the details.  By relying on Andy to “manage the minutia,” I was able to stay more relaxed and less stressed.

Finally, I had an epiphany that, in order for this process to be successful, I’d have to stop expecting infertility to somehow fit into my life.  I don’t know about you, but I was pretty overwhelmed by all we had on our plates.  At first, I was trying to squeeze in my appointments with PFC and with my fertility acupuncturist, while maintaining a calendar filled with dinners with friends, a busy work schedule, and a significant amount of travel. It’s no surprise that I was tired and stressed out, but I also became very resentful.  I was seeing a fertility acupuncturist on a weekly basis, yet I was annoyed that she recommended I take herbs and make changes to my diet.  I was frustrated as I tried to find time for all the appointments at PFC. Then, one night I was crying and sharing my frustrations with Andy, and he helped me see things differently.  He said that none of this was going to work if I didn’t fully embrace what we were doing.  I had to take the herbs with a positive attitude and whole-heartedly believe in the power of both eastern and western medicines.  Otherwise, what was the point in going through it all?  I realized that my bad attitude could have the power to neutralize all we were doing and I had to shift my mindset, accept that this was our path, and surrender to the process.  I created a big opening in my life so that there would be space for the infertility and all the energy it would take to tackle it.  I stopped traveling, dramatically reduced my social commitments, and spent much more time resting and “nesting” at home.  This was really difficult for me as an extrovert, but it became so much easier to make the right decisions and to more graciously accept what was required of me.

The last thing I would like to mention is that we were not secretive or private about our challenges with infertility.  I’m used to being pretty open with my friends, and I think it helped us to reach out to people for support during our ups and downs. One friend in particular, who had gone through her own IVF process, was reading some message boards online and found out about a new form of preimplantation genetic testing that she thought might be helpful to us.  We brought it up to Dr. Chenette and he was happy to give it a try since our prior IVF rounds produced seemingly good embryos, but failed to result in a viable pregnancy. So, on our 3^rd round of IVF, on day 3 we had 12 great looking embryos.  PFC biopsied all 12 and Gene Security Network ran a full analysis of all 23 sets of chromosomes.  On day 5 we showed up to transfer the best ones.  We were excited because we would know which embryos were genetically viable and which were not.  As we waited to see Dr. Givens, we wondered whether we would have 2 or 3 embryos to transfer.  But when Dr. Givens entered the procedure room, we could tell something was wrong.  We were told that all 12 of our embryos were genetically defective and none were viable for transfer.  Worse yet, because all of them possessed defects from the maternal chromosomes, it was recommended that we stop trying to conceive with my eggs and to think about alternative paths.  It seemed that this path had come to an end.  None of our embryos were good and there was no point in trying to make any more.  The news was devastating for us.

Andy and I went to a dark place for a few weeks.  But I’m happy to say that after talking and crying and praying about our situation, we came out of the darkness fully ready to embrace the process with an egg donor as soon as possible.  But first, we wanted to do the same preimplantation genetic testing on the 4 frozen embryos we had saved from our 2^nd round of IVF.  As expected, 3 of those embryos were genetically defective, just like the 12 from our 3^rd round of IVF.  But, we also experienced a miracle: one of those embryos was a genetically perfect boy.  He was my last hope to have a baby with my own genetic make-up.  Amazingly, he survived the freeze and the thaw, and survived the biopsy for the testing.  We transferred him in April and today I hit 37 weeks of pregnancy.  He is now considered full term and we are excited to meet him soon!

So, that’s our story.  I know we all have one.  Andy and I wish you the very best as you pursue parenthood and aim to build your family in whatever way makes sense for you. 

~Andy and Susan Nelson

Update:

“Our son was born on 12/30/10 at 12:20 am.  His name is Boden, he weighed 6 lbs. 15 oz. at birth, was 20” long, and is completely healthy.”

The field of Assisted Reproduction has always been one of rapidly evolving technologies, but nowhere more so than in the area of screening embryos. Screening is possible for not only genetic disease (PGD) and but also abnormal numbers of chromosomes (PGS). Along with the revolution in human DNA biotechnology, new companies such as Gene Security Network of Redwood City, California have emerged.  They are able to apply information from the Human Genome Project to the analysis of DNA from single human embryonic cells.

It is now possible to accurately diagnose most any human genetic disease in a pre-implantation human embryo. We do not even need to know the mutated sequence as long as there is DNA available from the parents that carry the mutation. By using what are called “linked markers”, we can make an analysis from the amplified DNA from a single embryonic cell and compare it to the parental DNA to determine the likelihood that any one embryo received mutated copies from either parent. This analysis is done at the time of an IVF cycle when the embryos are in the IVF laboratory. Affected embryos carrying mutations that may cause the disease, such as cystic fibrosis or muscular dystrophy, are not transplanted back into the mother’s uterus.

Until recently, a single embryonic cell could only be analyzed for either a mutated gene sequence using a limited number of markers (usually about 10) or for chromosome copy number (karyotype), but not both at the same time. In the last year, Gene Security Network has offered testing of DNA for BOTH genetic mutations (when parents are at risk for having affected offspring) AND for chromosome copy number to rule out Down Syndrome, Trisomy 18, or any other “aneuploidies” that can cause implantation failure or miscarriage. Both tests can be done on the amplified DNA from a single cell. Pacific Fertility Center has been participating in their pilot studies on this project and, due to the success of the initial group of patients PFC is now offering this type of testing routinely to couples that need this service. We welcome this change because it means we can now not only select unaffected embryos, but also have a fairly high confidence that the embryos we select for embryo transfer have normal chromosome copy numbers and will have a good chance of establishing a normal pregnancy.

Another area in which this DNA micro-array technology has found application is in the area of testing miscarriages for chromosome copy number. In the past, if we wanted to know if the reason a miscarriage had occurred was due to abnormal chromosomes, we had to do a D&C procedure, obtain placental DNA and send it to a cytogenetics lab. At the cytogenetics lab, the placental tissue had to be put into cell culture to try to capture dividing cells, which is the only way a karyotyping analysis could be performed. If the placental tissue contained no viable, living cells, the culture would fail and there would be no results. If the analysis revealed a 46 XX karyotype, we could not be sure that this was a normal female miscarried or if the cell culture was contaminated with maternal DNA. Now we can send the placental tissue with a sample of the mother’s blood, and the lab can tell if the DNA is maternal or not and the tissue does not need to be viable to get a result. This then allows us to determine if a pregnancy loss was due to abnormal fetal chromosomes, one of the most common causes of miscarriage.

There is no doubt that all of these new genetic technologies will continue to evolve over time, becoming even more rapid and accurate than they are today. It is exciting to be involved with applying the latest science and biotech has to offer to help solve clinical problems for our fertility patients.

-Carolyn Givens, M.D.

Engaging in well designed and executed research in the world of fertility treatment can be very difficult.  However, in order to advance in our field, and to counsel patients about expeditious and cost-effective plans for success, we need to conduct research.  When patients are diagnosed with Unexplained Infertility, it is both frustrating for the patient (why can’t my doctor figure out what’s wrong with me?), and for the treating physician (we like to be able to “show” where the problems are).  We have known for 10 years now, from a well designed study by Guzick and his team, that for patients with Unexplained Infertility the chances of success with “low tech” treatment options are still in a low range of 5-12% per cycle.  This range is dependent on the female’s age and use of Clomid or gonadotropins (1) (Ryan, I; A Most Frustrating Diagnosis (2)).  Now we have insight into comparing cost effectiveness of low-tech options (Clomid or gonadotropin therapy) versus IVF treatment (3).

The FASTT study started in September 2001 with 503 women between the ages of 21-39,   the average age was 33, and continued until April 2006.  A few months ago the final results were published, after a nine-year process.  The study took place at Boston IVF Center in Massachusetts, a state where fertility treatment is a covered health insurance benefit, including up to six IVF cycles.  After a full fertility evaluation confirmed that the couples had Unexplained Infertility, the patients were enrolled in the study.  Patients were randomly assigned to one of two treatment plans: 1) Three cycles of Clomid plus intra-uterine insemination (IUI), followed by 3 cycles of gonadotropin/IUI, then up to 6 IVF embryo transfer cycles (Conventional treatment), or 2) Three cycles of Clomid/IUI followed by up to 6 IVF embryo transfer cycles (Accelerated treatment).  All treatment protocols, medication dosing, and number of embryos transferred were practiced similarly among the patients.  In addition, the patients kept a diary of additional time and money spent in each treatment cycle.  This cost included time away from work, medication co-pays, and payment for additional care (e.g. emotional counseling). A financial analysis of the total charges incurred for each patient from the time of entry into the study until the patient had a delivery (including pregnancy and newborn care); the patient stopped treatment; or the study was closed.  The study’s two primary endpoints were comparing: 1) time to pregnancy, and 2) health care costs associated with that pregnancy/delivery.  Secondary endpoints were per-cycle pregnancy rates, per-couple pregnancy rates, and adverse outcomes.

Sixty-four percent of couples delivered at least one live-born baby by the close of the study in 2006 (150 conventional and 171 accelerated). The time-to-pregnancy was statistically shorter for the accelerated group compared to the conventional group.  The estimated time-to-pregnancy was 8 months in the accelerated arm and 11 months in the conventional arm.  This 3-month difference between the two groups would suggest that the additional 3 months doing gonadotropin/IUI cycles did not contribute to a shorter time-to-pregnancy than the 3 Clomid/IUI cycles alone.

Per-cycle pregnancy rates for Clomid/IUI, gonadotropin/IUI and IVF were 7.6%, 9.8% and 30% respectively.  The very slight increase seen in the gonadotropin/IUI rates did not have any impact on the “time-to-pregnancy rates” (as noted above), and yet are much more costly cycles than a Clomid/IUI cycle (average $500/cycle vs. $2500/cycle).

In the Guzick study, the greatest number of High Order Multiple (HOM) pregnancies (triplets or greater) was in the gonadotropin/IUI cycles.  This finding has been echoed by a number of other studies.  In the FASTT report, there were an equal number of HOM pregnancies in each group.  In the conventional group, there were two sets of triplets, both from gonadotropin cycles.  In the accelerated group, there were 3 sets of triplets, one from Clomid, and two from IVF.  The average number of embryos transferred in the IVF group was 2.3.  With the improvement in IVF laboratory techniques, many IVF centers currently advocate for transfers of only one embryo in women with an average age of 33.  This practice trend will likely decrease the number of HOM in IVF, and would most likely present further benefit (safety and financial) to the accelerated strategy.

A cost effective analysis shows the total charges per delivery to be $9,846 lower for the accelerated group ($61,553 per delivery) than the conventional group ($71,399 per delivery).  If the analysis is limited to charges of infertility treatment per delivery, the difference was $5,802 in favor of the accelerated arm.  The observed incremental difference in charges per couple was a savings of $2,624 for the accelerated treatment, and an increase in the proportion of couples with deliveries of 0.06.  In the parlance of cost-effectiveness analysis, accelerated treatment dominates conventional treatment.  This analysis holds true as long as the charges of an IVF cycle are <$17,749 (which, even in today’s dollar, is a realistic expectation for patients in their early 30s).

In summary, for patients with Unexplained Infertility, doing 3 cycles of gonadotropin/IUI after 3 cycles of Clomid/IUI was of no added benefit.  Accelerated treatment to IVF saves money and results in a greater proportion of couples with delivery of a live-born baby.  In terms of the financial benefit, the charges for treatment, pregnancy and delivery were less for couples in the accelerated arm compared to the conventional arm. 

Pacific Fertility Center strives to provide patients with treatment recommendations and protocols based on sound science.  We appreciate and are thankful to our IVF colleagues who have the tenacity and ability to proceed with studies such as this FASTT study.  We all benefit from their efforts!

Isabelle Ryan, MD

(1)   Guzick et al.  Efficacy of superovulation and intrauterine insemination in the treatment of infertility, N Engl J Med 1999;340:177-83

(2)     Ryan, I; A Most Frustrating Diagnosis; June 2009, Fertility Flash Science Pulse, Vol 7, issue 4; http://www.pacificfertilitycenter.com/fertilityflash/vol7_issue4.htm#Article1

(3)   Reindollar et al.  A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial, Fert Ster 2010; 94:3,888-898

Endometriosis was a puzzling disease when first described by pathologist Rokitansky in 1860. Though we now have a clearer understanding of some aspects of the biology of this disease, it still remains largely a mystery 150 years later.

Endometriosis affects about 5 million women in the U.S. Of women with infertility, approximately 25% are diagnosed with endometriosis. The symptoms fall into two categories: 1) pelvic pain, most significantly with menses, and 2) infertility. The definitive method to diagnose this disease is surgery. A laparoscopy is performed to obtain tissue biopsies of typical peritoneal lesions (peritoneum is the internal layer overlaying pelvic organs including the uterus, fallopian tubes and ovaries); and confirm the presence of endometrial glands in those biopsies. The American Fertility Society has created a classification scheme which grades the disease (Grade I-IV). It is important to understand that there is not necessarily a correlation between pelvic pain and the severity (or grade) of the disease. Another method for presumptively diagnosing endometriosis is with ultrasound, if the patient has endometriosis ovarian cysts (endometriomas), or with MRI if one there is endometriosis growth in the
uterine muscle layer (adenomyosis).

A diagnosis of even minimal to mild endometriosis (stage I and II) can have significant consequences on fertility success rates. A fertile 30 year old woman has about a 25% chance of pregnancy per month (fecundity rate). A patient diagnosed with minimal to mild endometriosis has about a 3% monthly fecundity rate (1, 2, 3). If surgery is performed to dissect and remove the visible endometriosis lesions, the fecundity rate improves to 6%; but this is still much lower than the 25% afforded a fertile 30 year old. If that same patient undergoes ovarian stimulation and insemination cycles, her monthly fecundity rate increases to 11% (4). If the combination of ovarian stimulation/IUI treatment is going to increase chances of pregnancy, results are usually seen within the first 3-4 treatment cycles. Undergoing additional IUI cycles is not typically beneficial, and proceeding to in-vitro fertilization (IVF) treatment would be the next step. For patients with severe endometriosis, gonadotropin/IUI therapy is of minimal assistance. Most patients with moderate to severe endometriosis (stage III and IV) will need to pursue IVF therapy (5).

IVF studies from the 80s and 90s indicate that patients with endometriosis have a slightly lower chance of achieving a pregnancy than patients with other infertility diagnoses (6). With current IVF laboratory techniques and current ovarian stimulation strategies, this difference will probably disappear—but up-to-date studies are needed as proof. When assessing if the lower pregnancy rate is because of a uterine or ovarian issue, it appears that the uterus of endometriosis patients is effective in providing a supportive environment for the embryo to attach (7). However, the oocytes (eggs) from endometriosis patients, particularly those with endometriomas, seem to have some compromised quality (8). This lower egg quality seems to lead to less healthy and effective embryos, and therefore overall lower pregnancy rates.

We clearly understand that strategies of suppressing endometriosis growth by using medications such as birth control pills, Danazol, Lupron or others, does not lead to improved pregnancy rates (9). The concept of a fertility “rebound” post-medical suppression has been proven false over-and-over again. These strategies only lose potentially precious time for the patient. Similar strategies of using medical suppression post surgical removal of endometriosis also fail to improve fecundity rates. The best approach is to move forward with an appropriate form of fertility treatment as soon as the patient desires fertility.

How to treat endometriomas has been debated, but we now have some studies to guide us. Collectively these studies indicate that patients who have undergone surgery for their endmetrioma(s) have the same IVF outcomes as those where the endometrioma(s) was left alone (10). We feel that the patient’s current clinical situation should be scrutinized carefully before recommending ovarian surgery for a patient who is seeking fertility. With surgical removal of an endometioma (ovarian cystectomy), we know that the ovary where surgery is performed will have fewer eggs and less normal ovarian tissue post surgery (11). This implies that we will have a lower chance of gathering eggs in an IVF cycle. Additionally, the patient will have a greater chance of having an elevated FSH after a cystectomy procedure, especially if she undergoes cystectomies of both ovaries (11). The risk of premature ovarian failure (POF or premature menopause) for a patient undergoing cystectomies of both ovaries for endometriomas is about 2% (12).

Historically the strategy for treating endometriosis has been to surgically remove or hormonally suppress its growth with various medications. As we better understand the biology of this disease, we can use more targeted therapies which interrupt the biochemical pathways that promote the growth of endometriosis lesions: aromatase inhibitors, estrogen and progesterone receptor blockers, angiogenesis inhibitors, etc. All of these types of medications are being studied in endometriosis patients. The future may hold some promising new medical options.

In summary, endometriosis clearly affects fecundity rates, even with minimal and mild disease. Using hormonal medications to suppress endometriosis provides no improvement in pregnancy rates, and surgical intervention provides minimal improvement. Most patients will need to pursue fertility treatment. For patients with moderate to severe disease, they most often will need to pursue IVF. For patients with endometriomas, careful consideration has to be given to all factors (age, assessment of egg quality, prior fertility treatment, etc.). The patient needs to be fully counseled prior to surgery, including risk of diminished ovarian quality (DOR) and premature menopause (POF). Patients with adenomyosis seem to have impaired implantation rates, and those with severe adenomyosis may need to consider a gestational carrier. Having a clear understanding of endometriosis as it impacts fertility, and having realistic expectations with each treatment type is most important when choosing fertility treatment options.

– Isabelle Ryan, M.D.

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