#397 ‒ Endometriosis and adenomyosis: diagnosis, fertility, reproductive aging, and emerging treatments | Renato Tomioka, M.D., Ph.D.
Dr. Renato Tomioka, an expert in reproductive medicine, discusses endometriosis and adenomyosis, conditions affecting millions of women. He explains diagnosis, treatment options, the impact of age on fertility, and common misconceptions, emphasizing early diagnosis for better outcomes.
Deep Dive Analysis
20 Topic Outline
Introduction to Endometriosis and Uterine Layers
Endometriosis Prevalence, Infertility Link, and Etiology
Biology of Endometriosis: Estrogen, Progesterone, and Oncogenic Traits
Understanding Adenomyosis and its Distinction from Endometriosis
Clinical Presentation of Endometriosis: The Six D's of Pain
Differentiating Adenomyosis from Endometriosis Symptoms
Uterine Fibroids: Classification and Clinical Impact
Mechanisms of Endometriosis Pain and Central Sensitization
Rising Prevalence of Endometriosis in Young Women and Diagnosis Delay
Modern Diagnostic Methods: Specialized Ultrasound and MRI
Treatment Strategies: Pain Relief vs. Fertility Preservation
Surgical Considerations and Recurrence Rates for Endometriosis
Infertility Workup and Mechanical vs. Molecular Factors
Managing Adenomyosis for Improved IVF Outcomes
Funding Gap in Endometriosis Research
Common Mistakes in Endometriosis Surgical Management
Misconceptions about Female Fertility and Age
Elective Egg Freezing: Timing, Success, and Economic Factors
Emerging Fertility Technologies and Future Outlook
Importance of Early Diagnosis and Treatment for Endometriosis
7 Key Concepts
Endometriosis
A chronic disease where endometrial-like tissue (stroma and glands resembling the uterine lining) grows outside the uterus, commonly on fallopian tubes, ovaries, bowel, bladder, or diaphragm. It affects about 10% of reproductive-aged women and contributes to infertility in 30-50% of cases.
Adenomyosis
The presence of endometrial-like tissue specifically within the myometrium (muscular wall) of the uterus. It is often called 'internal endometriosis' but has distinct molecular pathways and is potentially more prevalent than endometriosis, affecting up to 20-30% of women.
Retrograde Menstruation
The process where menstrual flow goes backward through the fallopian tubes into the pelvis. While 90% of women experience this, only 10% develop endometriosis, suggesting immune dysregulation or other factors are also necessary.
Progesterone Resistance
A characteristic of endometriotic lesions where the progesterone receptor is downregulated, requiring much higher levels of progesterone to produce its effect. This contributes to the estrogen dominance seen in these lesions.
Central Sensitization (Nociplastic Pain)
A type of chronic pain where the nervous system's wiring changes due to prolonged pain, causing even minor stimuli to trigger severe pain. This can occur in endometriosis patients, making pain persist even after successful lesion removal.
Aneuploidy
An abnormality in the number of chromosomes in an egg or embryo, typically resulting from errors in meiosis on the maternal side (93-95% of cases). Most aneuploid embryos are not compatible with life or result in miscarriage, with rates rising exponentially after age 35.
Mitochondrial Replacement Therapy
A technology where the nucleus (containing genetic material) from a parent's embryo is inserted into an enucleated donor oocyte that has healthy mitochondria. This is used to prevent mitochondrial disease, not to solve age-related chromosomal problems.
10 Questions Answered
Endometriosis is a chronic disease where tissue similar to the uterine lining grows outside the uterus, affecting about 10% of reproductive-aged women and often leading to infertility.
Adenomyosis involves endometrial-like tissue growing within the muscular wall of the uterus (myometrium), while endometriosis involves this tissue growing outside the uterus in other pelvic organs.
Endometriosis typically presents with 'the six D's': dysmenorrhea (painful periods), deep dyspareunia (pain during intercourse), dyschezia (painful bowel movements), dysuria (painful urination), difficulty conceiving (infertility), and dysfunctional chronic pelvic pain.
Diagnosis is frequently delayed due to cultural normalization of female pain, lack of simple biomarkers, and the traditional reliance on invasive diagnostic laparoscopy, which is now often replaced by specialized imaging.
No, a normal transvaginal ultrasound has very low sensitivity for detecting endometriosis, especially superficial lesions, and does not rule out the disease. Specialized ultrasound with bowel prep or MRI is required.
Female age is the most significant factor, as aneuploidy (chromosomal abnormality) rates in eggs rise exponentially after age 35, making conception and live birth increasingly difficult due to higher rates of miscarriage and implantation failure.
Surgery can provide relief and improve fertility, but it's not a cure. Endometriosis has a high recurrence rate if not followed by hormonal therapy, and surgery can sometimes reduce ovarian reserve.
Damaged fallopian tubes (hydrosalpinx) can reduce IVF success rates by half, even if embryos are implanted directly into the uterus, due to mechanical effects and the release of embryotoxic cytokines.
The success rate of egg freezing depends heavily on the woman's age at the time of freezing and the number of eggs retrieved; for example, 15 eggs frozen at age 25 offer over an 80% chance of at least one baby, but the cost-effectiveness is often better around age 32-35.
No, mitochondrial replacement therapy addresses mitochondrial diseases by swapping the cytoplasm of an egg, but it does not solve the primary problem of age-related chromosomal abnormalities in the egg's nucleus.
9 Actionable Insights
1. Challenge Pain Normalization
Do not accept the cultural normalization of female pelvic pain as ’normal’ or ‘just your regular period.’ Seek a second opinion if symptoms like severe dysmenorrhea, dyspareunia, or chronic pelvic pain are dismissed.
2. Request Specialized Imaging for Endometriosis
If endometriosis is suspected, request a specialized ultrasound with bowel prep or an MRI, as a normal transvaginal ultrasound has very low sensitivity and may miss the disease.
3. Consider Hormonal Therapy Post-Surgery
After endometriosis surgery, use hormonal treatment like a Mirena IUD to significantly reduce the recurrence rate, as surgery alone is often insufficient for long-term control.
4. Avoid Unnecessary Endometrioma Surgery for Fertility
Do not surgically remove ovarian endometriomas (cysts) if fertility preservation is a priority, as stripping them can damage healthy ovarian tissue and reduce AMH (ovarian reserve).
5. Remove Damaged Fallopian Tubes Before IVF
If fallopian tubes are damaged (e.g., hydrosalpinx), surgically remove them (salpingectomy) before IVF, as leaving them can reduce IVF success rates due to embryotoxic effects.
6. Address Infertility as a Couple’s Disease
When investigating infertility, always include a male factor workup (e.g., sperm analysis) alongside female investigations, as it is a condition affecting both partners.
7. Recognize Age as the Primary Fertility Factor
Understand that female age is the most critical factor in fertility, with aneuploidy rates rising exponentially after age 35, often leading to miscarriages or implantation failure even with normal exams.
8. Understand Human Reproduction Inefficiency
Be aware that human reproduction is inherently inefficient; even at prime reproductive age (25), not all eggs are euploid, and many fertilized embryos will not develop into blastocysts or implant successfully.
9. Consider Egg Freezing for Timeline Uncertainty
If a woman is in her late 20s to early 30s and uncertain about her timeline for having children, consider checking AMH levels and discussing elective egg freezing to preserve fertility, acknowledging the J-curve of aneuploidy rates.
6 Key Quotes
Endometriosis is a disease, a chronic disease, where an endometrial-like tissue, very similar to the endometrial, is outside the uterus.
Renato Tomioka
If you do a normal ultrasound and you don't have endometriosis in the report, doesn't mean that you don't have endometriosis. That's one of the most important things, I think, in this episode.
Renato Tomioka
Imagine like endometriosis lesion is a burglar. So surgery can remove the burglar. Hormones can lock the door. But once you have this alarm system ringing and ringing years after years, the wiring changed. And now even a wind can, you know, trigger the alarm.
Renato Tomioka
Age is the most important factor. And even doctors don't just, they just don't realize it.
Renato Tomioka
Reproduction in humans, it's very inefficient.
Renato Tomioka
The cases that stay with me are not the most complex surgeries, not the difficult IVF cycles. There are those women that cry, not from pain, but during the appointment from relief. They finally have a diagnosis.
Renato Tomioka
2 Protocols
Specialized Ultrasound Protocol for Endometriosis Diagnosis
Renato Tomioka- Perform bowel prep (e.g., enema) one hour before the exam.
- Follow a no-residue diet prior to the exam.
- Use gel inside the vagina to enhance visualization.
- An expert radiologist or specialized gynecologist performs the detailed scan, looking for small lesions in the bowel, bladder, and assessing bowel layers.
- Utilize the 'sliding sign' by pushing the probe against the posterior vaginal wall to check for adhesions and uterus mobility.
Adenomyosis Treatment Before IVF Transfer
Renato Tomioka- Confirm diagnosis of adenomyosis, especially after failed IVF transfers.
- Administer a GnRH analog (agonist, e.g., Lupron or goserelin) via monthly subcutaneous injections for 2 to 4 months.
- During this period, the medication suppresses ovulation and estradiol levels, inducing menopause-like symptoms.
- After the suppression period, proceed with embryo transfer using minimal estrogen and high amounts of progesterone.