Endometriosis and Reproduction: What We Have Learned.

Garcia-Fernandez J, Jaime Garcia-Fernandez, Jaime García-Fernández, García-Velasco JA, Juan A. García-Velasco
The Yale journal of biology and medicine · 2020 · vol. 93(4) , pp. 571–577 · PMID:33005121 · PMC7513434 · W3090919070
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This review details how ovarian damage, specifically quantitative impairment, is the primary fertility compromise in endometriosis, and discusses ovarian surgery and fertility preservation considerations.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-09 · read from full text ⓘ

This mini-review discusses what is known about how endometriosis affects fertility, emphasizing evidence from assisted reproductive technology, fertility markers, and the consequences of ovarian surgery. It highlights that the main damaging mechanism is a quantitative impairment of ovarian reserve (lower AFC and AMH, especially in advanced/bilateral ovarian disease), while endometrial receptivity is presented as not apparently affected, and it notes that surgery can reduce ovarian reserve and ovarian stimulation response without clearly improving pregnancy chances when done before ART, with explicit caveats that clinical variability and correlations (e.g., ASRM stage with fertility) are imperfect. It also describes multiple proposed fertility-limiting mechanisms beyond ovarian reserve and contrasts the less predictive ASRM staging with the more detailed Endometriosis Fertility Index (EFI). This paper is centrally about endometriosis — it reviews endometriosis-related mechanisms compromising reproduction and summarizes impacts on ovarian reserve, surgery, and ART outcomes.

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Abstract

Endometriosis, despite only affecting 10-15% of women of fertile age, is still an enigmatic disease. Recent developments in assisted reproductive technology have contributed to a better understanding of where and how endometriosis could compromise fertility. In this mini-review we will show how the main point of damage in endometriosis is quantitative impairment of the ovaries, if the "less is more" mantra should be applied when considering ovarian surgery, and when fertility preservation prior to ovarian surgery could be considered. Endometrial receptivity, however, does not seem to be affected.
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Intro

Although endometriosis was described in the late 1800s, we still do not fully understand why this progressive disease, characterized by the appearance of endometrial tissue – glands and stroma – outside the endometrial cavity, is present only in some women and not in others. Its huge clinical variability in symptoms and technical difficulty to diagnose precisely in its early stages makes diagnosis only possible when the disease is quite advanced and already producing pelvic pain and/or infertility in patients [ 1 ]. Still today, there is a 5- to 10-year delay from the onset of symptoms to the clinical diagnosis of endometriosis [ 2 ]. It affects around 10-15% of women of fertile age, so it is not an uncommon disease that may be present in women from menarche to menopause, and even in women beyond menopause, in some exceptional cases [ 3 ]. Unfortunately, early stages of the disease will cause very unspecific symptoms, mainly pelvic pain. It represents one of the most common causes of chronic pelvic pain, dysmenorrhea, and infertility [ 4 ]. This pain may impair the quality of life of affected women, especially with their partners, their families, and at work. Endometriotic lesions will grow within the peritoneum and ovaries, and the fibrosis induced by this will affect nerve fibers causing pain. These endometriotic lesions are influenced by the menstrual cycle, as they have both endometrial glands and stroma. Thus, in each menstruation the lesions may bleed, causing inflammation and fibrosis in the nearby tissues, such as ovaries, pelvic organs (ureter, bladder, bowel, and intestines), pelvic peritoneum, and/or rectovaginal septum [ 4 ]. Thus, endometriosis can be divided into three main types: peritoneal , deep infiltrating , and ovarian , and these frequently coexist [ 5 ]. But, unless the physician has endometriosis in their differential diagnosis of pelvic pain in young women, the patient will be treated with pain killers, non-steroidal anti-inflammatory drugs (NSAIDs), or even oral contraceptive pills (OCPs), in order to minimize pelvic pain and dysmenorrhea. Medical therapy is aimed at alleviating the symptoms and reducing the size of the lesions, thus improving the patient’s quality of life [ 6 ]. Although many drugs and minimally invasive techniques with different side-effects have been tried to date, no agent has been found to be objectively superior to the rest. In fact, given that most interfere with estradiol secretion and ovulation, they may interfere with fertility as well. A very common practice was to administer a depot of gonadotropin releasing hormone (GnRH) agonist, leading to down-regulation of GnRH receptors and generating a hypogonadotropic hypogonadism state in the body, hence improving the endometriotic lesions due to low estradiol levels [ 6 ]. New oral GnRH antagonists, which do not completely suppress estradiol secretion, may be an alternative with less side effects than the agonists [ 7 ]. Oral Contraceptive (OC) pills have been shown to have beneficial effects due to their suppressive action [ 8 ]. Progestins are also an option in patients with endometriosis due to their anti-proliferative and anti-inflammatory properties [ 8 ]. Resveratrol, among other natural remedies, is a natural phytoalexin synthesized by plants in response to ultraviolet radiation and fungal infections which has been proposed as potential treatment for endometriosis due to its anti-inflammatory, anti-oxidative, and anti-angiogenic properties [ 8 ]. Finally, minimally invasive surgery is usually the best option for women with extensive endometriosis and excruciating pain [ 3 , 9 ]. Careful laparoscopic excision of the endometriotic lesions and scar tissue, avoiding damage to the surrounding tissues, will in most cases, reduce pain and improve quality of life. Special care should be taken when removing lesions from the ovaries in order to avoid reducing the ovarian reserve in young women. In fact, spontaneous pregnancy after surgery in a population of women with severe endometriosis may be up to 73% [ 3 ], but this may not be exactly the same in infertile women with endometriosis.

Discussion

Endometriosis is a progressive disease, although progression varies among individuals [ 11 ]. As we are currently unable to predict which patients will have a very aggressive growth of their disease, there is a tendency to treat young women diagnosed with endometriosis with either progestins or oral contraceptive pill in a continuous protocol – without placebo – in order to avoid the monthly bleeding, and hypothetically, contributing to the control of the disease. However, recurrence of the disease may happen even under these hormonal treatments [ 42 ]. Fertility preservation is an attractive alternative which gives women the option of having a child with their own gametes when they are at risk of premature depletion of their ovarian reserve. The first indication for this were oncological patients, especially those receiving alkylating agents causing high risk of premature ovarian failure as a secondary effect [ 43 ]. Today, fertility preservation is discussed prior to their oncological treatment and those who opt to freeing their oocytes, in case they enter premature menopause after the chemotherapy, can have their own children without considering oocyte donation [ 43 ]. Still, the return rate – women who froze their oocytes and after failing to conceive at home spontaneously, came back to use their oocyte in an IVF cycle – is low: 6 to 12%. Some women do get pregnant spontaneously, some do not survive the disease, for others it may still be too early for them to use their frozen oocytes, and some will never come back to use them [ 43 ]. Another indication are women who decide to postpone maternity for many different reasons [ 44 ]. Here also the return rate is still low. Our group recently published the first study on fertility preservation in women with endometriosis. Being a progressive disease, women with endometriosis are at risk of premature reduced ovarian reserve, so oocyte vitrification is a valid alternative to increase their reproductive chances. We recently analyzed data from 485 women who underwent fertility preservation for endometriosis at our institution [ 45 ]. Mean age was 35.7 years, and those patients who underwent surgery prior to oocyte freezing had a younger age (33.4 vs 36.7 years, p <0.05). The number of oocytes obtained, as well as the cumulative live birth rate, was significantly higher in women who vitrified their oocytes before surgery, and not after surgery. In this group of patients, we observed a higher return rate than in oncological patients or social freezers, which could suggest that, in these patients, the vitrification of oocytes was performed as an adjuvant option within the treatment of endometriosis-related infertility. Thus, the advantage of fertility preservation in young women with endometriosis is that they can obtain a good number of mature oocytes, and especially if the procedure is done prior to surgery.

Conclusions

Endometriosis has been described for many decades, and it has been often linked to infertility. The impact of endometriosis on fertility is mainly quantitative damage to the female reproductive tract, reducing ovarian reserve, oocyte and embryo quality, and quality of life, thus interfering with fertility. Even though there is a biological rationale for a lower oocyte quality as shown in basic research, this does not seem to translate when clinical data is analyzed. Treatments should be tailored carefully, as surgery does not improve the results of ART. It should be carefully performed when the patient is symptomatic, as it may further reduce their ovarian reserve. Today, fertility preservation could be discussed with the patient prior to their surgery so they could vitrify their oocytes and have a valid alternative to have children in case surgery and/or disease progression compromises their ovarian reserve.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Fertility Preservation Female Fertility Humans Reproduction Reproductive Techniques, Assisted

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