Endometriosis is a condition where the lining of the uterus grows in other places besides its usual spot inside the uterus. It can affect the Fallopian tubes, ovaries, and bowel and on rare occasions can even disseminate beyond the pelvis and abdominal cavity. While it may seem like a physical barrier to fertility is the main cause of infertility in endometriosis, this is an oversimplified view.

The truth is that even mild cases of endometriosis can make it harder to get pregnant. However, it doesn’t mean that women with this condition are completely unable to have children. Compared to women without endometriosis who ovulate normally and are the same age, women with mild to moderate endometriosis are about four to six times less likely to have a successful pregnancy.

Unfortunately, endometriosis commonly goes undiagnosed for many years. Women with this condition are often mistakenly labeled as having “unexplained infertility” until the lesions are seen during an abdominal-pelvic surgical procedure. It’s not surprising that many patients with “unexplained” infertility eventually discover they have endometriosis if they are followed over a period spanning several years.

The journey of women with endometriosis can be challenging, particularly when it comes to fertility. However, it’s important to remember that there is hope and numerous ways to overcome these obstacles. 

Reasons Behind the Impact of Endometriosis on Fertility

• Toxic Pelvic Environment: Endometriosis creates a toxic pelvic environment that can compromise the fertilization process. Even women with mild to moderate endometriosis, whose fallopian tubes are usually healthy, face difficulties in conceiving due to exposure to peritoneal toxins. Unlike what some believe, surgical intervention or medication alone cannot eradicate this toxic influence. Visible endometriotic deposits are just the tip of the iceberg, as numerous translucent deposits produce toxins that impact fertility. Consequently, surgical removal of visible deposits or other treatments such as controlled ovarian stimulation (COS) with or without intrauterine insemination may not improve the chances of pregnancy. In such cases, IVF is the most effective method to enhance pregnancy potential by protecting eggs from exposure to toxic pelvic environment.
• Ovulation Dysfunction: Approximately 25-30% of endometriosis cases are associated with ovulation dysfunction. This often requires COS in an attempt to increase the chances of pregnancy. Unfortunately, the toxic pelvic environment often diminishes the effectiveness of anything other than in vitro fertilization (IVF) in enhancing pregnancy potential. Although this may seem disheartening, IVF offers great hope for women facing this challenge.
• Pelvic Adhesions and Tubal Damage: Advanced endometriosis can lead to pelvic adhesions and scarring, which damage, immobilize or obstruct the fallopian tubes, preventing the union of sperm and eggs. This can present a significant obstacle to fertility.
• Endometriomas (chocolate cysts): Advanced endometriosis often involves the development of ovarian cysts called endometriomas or chocolate cysts. These cysts contain altered blood and can be large and multiple. When these endometriomas grow larger than 1cm, they can activate surrounding ovarian tissue leading to the local production of excessive male hormones such as testosterone. This hormonal imbalance can compromise egg development and increase the likelihood of chromosomal abnormalities, reducing the competency of eggs and embryos. Therefore, eliminating such cysts surgically or by sclerotherapy (see below) before pursuing IVF is strongly recommended.
• Immunologic implantation dysfunction (IID): Endometriosis, regardless of its severity, is associated with immunologic implantation dysfunction (IID) in more than 30% of cases. This dysfunction (among other effects) involves the activation of uterine natural killer cells (NKa) and cytotoxic lymphocytes (CTL). These immune cells attack the developing embryo’s “root system” (trophoblast) as it tries to attach to the uterine wall, often resulting in undetected early losses, chemical pregnancies and miscarriages. Understanding this aspect of endometriosis-related infertility is crucial to provide appropriate care and support.

While advanced endometriosis can cause significant anatomical damage and infertility, it’s important to note that the quality of life for these patients is often severely compromised by pain and discomfort. In such cases, the priority may shift towards finding relief from symptoms through medical and surgical treatment options, thereby deferring or (sometimes) even precluding future pregnancies.

For patients with moderately severe endometriosis, there is a moderate amount of scarring, adhesions, and endometriotic deposits. However, the fallopian tubes are usually open and functional, offering a chance (albeit markedly reduced) of natural conception.

Uncommon Symptoms of Endometriosis and Diagnosis

The identification of endometriosis as the cause of Infertility starts with having a high index of suspicion. Symptoms such as heavy/prolonged and painful menstruation with painful deep vaginal penetration and ovulation pain along with difficulty in conceiving are strong suggestions of underlying endometriosis. A definitive diagnosis requires surgical  visualization of endometriotic lesions and/or pelvic adhesive disease, and/or ultrasound /MRI detection of ovarian endometriotic cysts. However, the exception of cases that require removal of endometriomas or urgent relief of incapacitating symptoms, successful treatment of the underlying infertility in most cases will not require such confirmation.  

It is also important to recognize that early endometriosis can be free of the uncommon symptoms and signs referred to above while still having a profoundly deleterious impact on fertility. A newer endometrial biopsy test (Receptiva/BCL-6) can help identify such women thereby avoiding the need for invasive trans-abdominal surgery (e.g., laparoscopy) to detect and diagnose the condition.  

Dismissing “unexplained infertility” solely on the basis of viable anatomical disease overlooks these crucial aspects and can hinder the hopes and dreams of many women facing endometriosis-related infertility.

Management of Endometriosis-related Infertility

When it comes to managing endometriosis-related infertility, there are several important considerations. Let’s explore these concepts to understand the available treatments and their potential for success.

1. Controlled Ovulation Stimulation (COS) with/without Intrauterine Insemination (IUI): The toxins present in the peritoneal secretions of women with endometriosis have a negative impact on fertilization potential, regardless of how sperm reach the fallopian tubes. This explains why COS with or without IUI does not significantly improve the chances of pregnancy compared to no treatment at all. In these cases, in vitro fertilization (IVF) is the most effective option to bypass these challenges and increase the chances of conception.
2. Pelvic Surgery: While laparoscopy or laparotomy surgery can aim to restore the anatomical integrity of the fallopian tubes, it does not address the negative influence of toxic peritoneal factors or the IID, often associated with endometriosis. Pelvic surgery is generally not recommended as a primary treatment for infertility related to endometriosis, especially for women over 35 years of age, as time is of the essence. However, for younger women who have more time on their side, surgery can be a viable option, with approximately 30% of women conceiving within a few years following corrective pelvic surgery.
3. Sclerotherapy for Ovarian Endometriomas: Sclerotherapy (often not a readily available medical service) offers a non-invasive, safe, and effective method to permanently eliminate ovarian endometriomas, without the need for invasive surgery. The procedure which involves draining the cysts and injecting a solution (e.g., tetracycline hydrochloride 5%) into the emptied cyst cavity, results in the disappearance of the lesions in over 75% of cases. This outpatient procedure is cost-effective, minimizes post-procedural pain and complications, and eliminates the need for laparoscopy or laparotomy.
4. Selective Immunotherapy: More than half of women with endometriosis have antiphospholipid antibodies (APA) that can hinder the development of the embryo’s “root system” (trophoblast). Additionally, about one-third of cases involve the activation of uterine natural killer cells (NKa) and cytotoxic lymphocytes (CTL), which can significantly impede implantation. Diagnostic tests which cannot be adequately performed by most laboratories and must be directed to a handful of Reproductive Immunology Reference laboratories in the United States, can identify such immunologic implantation dysfunctions (IID). Treatment options include heparinoids, such as Clexane/Lovenox, to improve IVF success rates in women with APA, and a combination of Intralipid (IL) and steroid therapy to down-regulate NKa/cytotoxic T-cells. IL therapy is a cost-effective alternative to Intravenous Gamma globulin (IVIg) with comparable efficacy and fewer side effects.
5. The Role of IVF: The toxic pelvic environment caused by endometriosis reduces natural fertilization potential. Consequently, women who are ovulating normally, have patent fallopian tubes and suffer from endometriosis are much less likely to conceive naturally or with fertility agents alone, including IUI. In such cases, IVF is the most effective approach to overcome the adverse pelvic environment and increase the chances of pregnancy. It is important to note that not all women with endometriosis require IVF, but for those > 35y for whom time is a serious consideration and for women with endometriosis (regardless of their age) where there are additional factors such male factor infertility, IID, or diminished or DOR, IVF is often is the treatment of choice.

In summary, while endometriosis can present challenges on the path to fertility, there is hope, IVF offers promising solutions to enhance pregnancy potential. With the right medical care, support, and understanding, women with endometriosis can embark on a journey towards fulfilling their dreams of starting a family.  

For young women under 35 years of age with endometriosis and who have adequate ovarian reserve , expectant treatment may be preferable if they have normal reproductive anatomy and fertile male partners. However, for older women or those with additional factors, such as pelvic adhesions, ovarian endometriomas, male infertility, IID, or DOR, IVF should be considered as the primary treatment option. 

While endometriosis can present challenges on the path to fertility, there is hope. Medical advances such as IVF, offer promising solutions to enhance pregnancy potential. With the right medical care, support, and understanding, women with endometriosis can embark on a journey towards fulfilling their dreams of starting a family. Contact us and explore the promising solutions of IVF to overcome endometriosis-related infertility.