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.

References

1. Jansen RP, Fertil Steril 1986; 46:141-3
2. Marcoux et al, NEJM 1997; Jul 24; 337(4):269-70
3. Parazzini, Hum Reprod 1999; 14(5):1332-4
4. Tummon et al, Fertil Streil 1997; 68(1):8-12
5. Dmowsky et al, Fertil Steril 78:750 2002
6. Barnhart et al, Fertil Steril 2002; 77:1148-1155
7. Diaz et al, Fertil Steril 2000; 74:31-34
8. Simon et al, Hum Reprod 1994; 9, 725-9
9. Hughes et al, Cochrane Database Syst Rev 2007; 3:CD000155
10. Tsoumpou et al, Fertil Steril 2009; 92, 75-87
11. Li et al, Fertil Steril 2009; 92(4):1428-35
12. Busacca et al, Obstet Gynecol 2006; (195), 4

I have pondered at length what my wildest dream would be if Oprah, or some other fairy godmother, were to grant it. Which famous person would I love to meet? What exotic location would I love to visit? Try as I might I cannot see past the sixth-month-old bundle in my arms. My baby girl and her three-year-old sister are my wildest dreams. Climbing Mt. Everest, running a marathon or meeting a superstar might be some people’s wildest dream, but for me conquering infertility and raising my daughters is my wildest dream.

At age 30 I started trying to get pregnant. I had endometriosis, I hadn’t used birth control for almost ten years and I had never been pregnant. I had also never imagined I would have difficulty conceiving. There was a great deal of irony in the amount of energy I put into trying not to get pregnant before my husband Red and I mutually agreed we were “ready”. After trying for more than a year, we went to see Dr. Carl Herbert and I was diagnosed with unexplained infertility. Thankfully, Dr. Herbert took excellent care of us and at age 34 I conceived my first daughter with the help of Clomiphene and IUI.

Conceiving my second daughter, however, proved more challenging, but was accomplished through IVF three years later. Even though I had tried IUI again and had produced many follicles, my IVF cycle revealed that the quality of my eggs was inferior. Dr. Herbert had the unhappy task of relating this distressing news to us during my embryo transfer, but he did so with tremendous grace and kindness. I have the utmost trust and confidence in Dr. Herbert and I feel blessed that he gave us the opportunity to conceive. Despite the quality of my embryos, we beat the odds and I conceived anyway. Yahoo!

Ultimately my goals were met, but it was the journey through infertility that has brought light and clarity into my life. With the help of my amazing doctor and with nurses like Ann McGovern (to whom I cried countless times), the laborious process of conceiving against the odds was made easier by their warmth and encouragement. I don’t know if it ever got “easier” being met with my period after each month’s unsuccessful attempt, however. By far the most searing memory, beyond all the shots and ultrasounds, was news, from what seemed like every woman on the planet, of other people’s pregnancies. And not only were they pregnant, but, their pregnancies were achieved unaided and on their first try. Of course!

What saved me and my marriage both times was a combination of therapy, friends and family. My husband was amazing through it all and our marriage is stronger and brighter as a result. When all is said and done and both my girls are strapped in their car seats or cuddling with me on the couch, all of the infertility effort seems like a distant memory. I feel so blessed to have conquered my infertility. My wildest two dreams have been realized.

– Jennifer

My infertility journey started when I was only 17. I was diagnosed with endometriosis and underwent my first laparoscopy. I had temporarily relief and then my symptoms returned. I tried various alternative treatments but they too offered only temporarily relief. This was not the life that I wanted to have as a young adult who wanted to have children more than anything in the world.

Surgery after surgery, specialist after specialist, my quality of life was slowly going down the drain. Initially, I told doctors that I didn’t want to have a hysterectomy but later, something had changed. I was eight surgeries into my journey and I asked my doctor if I could have just my uterus removed so I could still try and have a biological child. He said yes and I was quite relieved. After the surgery, I felt better for a while, but the pain still continued. I had to evaluate my life and decide what was important to me. I knew I wanted to live, but the pain had me in and out of the hospital and often times feeling suicidal. I had no other choice but to have my ovaries removed.

Luckily, I thought about freezing embryos and called Pacific Fertility Center. I met with Dr. Isabelle Ryan and she changed my life. My boyfriend and I knew we wanted to get married and I was on a limited time line until I had my ovaries removed. We only had one chance to do this and we were determined to do it right. We underwent one cycle of In Vitro Fertilization and froze all of our embryos. We froze our embryos at a 2PN stage* per Dr. Conaghan and Dr. Ryan’s request. This would help our chances of having them thaw better but we don’t know how they will turn out. We were willing to take that chance.

Two weeks later, I had my ovaries removed and then felt I was ready to move on with my life. My boyfriend and I got engaged and together dealt with the loss of having me carry our child. In our counseling session with Peggy Orlin, MFT at Pacific Fertility Center, we talked about what if a gestational cycle didn’t work. We knew that we would be parents no matter what and if it wasn’t our biological child we could be ok with that.

From time to time, I still grieve the loss of being pregnant, but know that I did everything that I could. Since then we have gotten married and have been offered the opportunity of a lifetime. A dear friend has said that she would like to carry our child. She has restored our faith in humanity. What an offer!

As we are working out the details, we are thankful for her commitment to us and our journey. We will transfer some of our embryos into our gestational carrier and hope for the best. Dr. Ryan and all of the staff at Pacific Fertility Center have been so supportive of us that we can’t wait to come back when we are ready to do our transfer.
Anonymous, San Francisco

* A note from Laboratory Director Joe Conaghan, PhD:
Embryos can be frozen at different stages of development, usually 1, 3 or 5 days after oocyte retrieval. In general, the earlier they are frozen, the better they tolerate the freezing process. Embryos frozen on day 1, or at the 2 pro-nuclei stage, survive freezing and thawing at a rate over 95%.

After trying “au natural” for several years, we were told to try clomid a few times… no luck. We were then told to try IUI but we decided against it. We always felt we had plenty of time but Daphne, my wife, had turned 36, and we knew we had to get serious.

Following a battery of tests, our picture went from bad to bleak. First we learned that my sperm count is lower than average, so I felt horrible. Then we learned that Daphne has endometriosis. So it was her turn to feel bad. You sort of feel like you’re letting the other one down.

Our OB/GYN decided we needed a specialized facility, and referred us to Pacific Fertility Center.

One of our toughest days was our first trip to San Francisco, a four-hour drive. We didn’t know anyone there. We went through the convolutions of testing and more testing and deciding to undergo IVF. And then minor surgery. This was in the middle of the holidays; Daphne felt sick, and we began thinking of all the expenses we had incurred just to get to that point. We felt like our lives were out of control. Standing on Pier 39, I wondered whether we could continue, and I said, “I don’t know if we can do this!” Daphne just looked haunted. She didn’t say a word.

Daphne was so meant to be a mother. At one point I started feeling desperate for her. Another mother in line at a grocery store yelled at her child, taking it all for granted. It just made us wonder why? Why them and not us? It made Daphne absolutely miserable.

During these tough times we would be comforted when we entered the doors of the center and felt a sense protection, as if people were putting their arms around us. We began to turn it around and started enjoying ourselves in the City while dealing with medication shots and appointments. We didn’t look back – and then it came time for the retrieval.

Just before Daphne was to receive the anesthesia, Dr. Schriock, with his soft-spoken mild manner came over to check in with us, and held her hand. That really touched her. If you’re going to go through something like this, you couldn’t ask for somebody more understanding. Whether they know it or not, the PFC physicians and nurses, and Joe come across as caring people before professionals, even though I know they’re experts.

We didn’t break any records; I think we barely made 10 embryos, but that gave us enough to use and freeze. Plus, they looked good.

After an agonizing wait, the news on our IVF cycle was negative.

We were disheartened, but Daphne quickly rebounded and we went right into our 2nd cycle – a frozen transfer. Again, the transfer, the waiting and again, negative.

Those were very black days. You feel part of a populace, but everyone is moving on and you’re not. You feel so alone. We were struggling so hard on an activity that should have been so natural. We were hostages to so many unknown factors.

We went on and did a 3rd try, again using our frozen embryos. We were fully prepared to be disappointed. After the transfer and the wait, the testing lab in Fresno drew her blood and by the time we got to our home close to Yosemite, the phone rang almost immediately. I was ready, standing next to my wife, forming the words that would comfort her, but instead she looked at me and gave me a thumbs-up!

From that time on, we were even more guarded than before… at least for a while. We were almost too afraid to tell people but we surprise-visited Daphne’s parents with a cake that said “We’re Pregnant!”

Tessa is now nearly two. Of course, you see children, and you know they’re considered perfect. But Tessa is the most photographed and beautiful baby, and she has a personality that just won’t stop.

We’re hoping to give Tessa a sibling soon with our remaining frozen embryos.

I now look back and see it kind of empirically – Tessa was one of the strongest embryos, and since being born, she hasn’t had any problems: no sniffles, no flu, not even a hiccup. So we didn’t just get a baby, she really is one of those babies!

– Randy Cohlan

Q:
Hi – I have severe painful endometriosis, am 34, otherwise healthy and fit with one failed fresh IVF cycle and one failed frozen transfer. Is there anyway I can help the process of implantation? And could the endometriosis be preventing the implantation? Many thanks for your help.

A:
Endometriosis is the condition where tissue that forms the uterine cavity lining each month (and is shed as menstrual flow is now growing outside of the uterine cavity. This extra-uterine tissue is most commonly found around the ovaries, fallopian tubes, and outer layer of the uterus. In general, the negative affects of endometriosis are due to processes occurring in the pelvis. These negative affects make the pelvic fluid more hostile to eggs and sperm. Therefore, the negative pregnancy affects are limited to the processes that are occurring in this pelvic environment (egg bathed by pelvic fluid as they are ovulated, fallopian tubes bathed by pelvic fluid and impacting fertilization and early embryo development). The uterine cavity itself seems to be protected from these negative affects. For patients who need to proceed to IVF, we bypass the “pelvic environment” and all steps which would be occurring in the pelvis are now occurring in the laboratory (egg recovery, fertilization, early embryo development). The uterus is protected from the negative pelvic affects, so pregnancy rates are the same for endometriosis patients, as they are for other patients who need IVF. Exceptions to this would be patients with adenomyosis. Adenomyosis is a benign condition characterized by the endometrium lining growing INTO the muscular layer of the uterus, instead of just staying confined to the uterine cavity. The other exception is for patients who have endometriomas (endometriosis ovarian cysts filled with thick, dark brown blood). These can impact egg quality, so it is not uncommon that if you have endometriomas, it might take a few more IVF cycles than the average to achieve a successful pregnancy.

Isabelle Ryan, MD  and Joe Conaghan, Ph.D contributed to this post