Ovarian Aging and the Alphabet Soup of Diagnoses: DOR, POI, POA, POF, and POR

Figure 1Image source1

Other day, I went to a masseuse for calming oil massage to feel relaxed and get restful sleep for a night. Although summer was away, hot flushes and night sweats were keeping me awake at night, so I thought of trying a good massage to help me sleep well.

The masseuse’s first response, “you are too young to experience such symptoms often accompanied with menopause.”

I smiled and told her “I look young that does not mean my ovaries are young too.”

My previous fertility doctor always says, “fertility is not skin deep, no matter how younger may look from outside or feel in great health, have most healthy lifestyle, your fertility health is not necessarily the same.”

Unless you pay attention, get evaluated and try for pregnancy, you will never know your true fertile potential.

I was young in my early thirties to be diagnosed with seriously depleting ovarian reserves. While I was trying to conceive, I remember completely exhausting scientific literature on ovarian biology and available fertility treatment options to rescue poor reproductive health. The medical acronyms on different disease states linked to ovarian aging are quite confusing for many of us and can easily make one feel hopeless.

Here is an excerpt of what you need to know as a fertility patient if you are diagnosed with advanced ovarian aging.

Basics of Ovarian Aging

In females, oocyte (follicles, egg) development begins and reaches its maximum in utero. There are approximately 6–7 million oocytes in a 20 weeks old fetus. At birth, only about 1–2 million oocytes remain and by puberty, approximately 300,000 oocytes remain. And as age progresses women lose oocytes at a steady rate.

Each month, only few of the follicles get selected from the oocyte pool and grow into mature follicles. And only one of the winning follicle releases egg every month, the rest of growing the follicles undergo apoptotic death (programmed cell death). Moreover, there is natural loss of oocytes that occur due to a phenomenon called “atresia” from the overall reserve. Women are programmed to lose eggs on a steady state.

As you can imagine, there are large variations in the number of oocytes within each woman, the rate of natural loss may be higher in some women that may make them run out of eggs sooner in their life span. When women completely deplete the reserves, menopause begins.

Unfortunately, scientists are limited in our knowledge of what controls this number or rate of loss but the available ovarian reserve certainly drives our fate to reproduce and a build a family.

The alphabet mystery of diagnosis:

Depending on the state of depletion of ovarian reserves, the conditions may be categorized into DOR (Diminished Ovarian Reserve) or Premature ovarian aging (POA), Premature Ovarian Insufficiency (POI).

DOR (Diminished Ovarian Reserve):

One of the common reasons for infertility in women is DOR, a medical condition in which women are left with fewer eggs than expected based on their biological age.

Currently, clinicians use a battery of tests to measure ovarian reserves that include blood level measurements for basal follicle-stimulating hormone [FSH], estradiol [E2], anti-mullerian hormone [AMH] and pelvic ultrasound for determining antral follicle count [AFC].

According to study published in 20153, a survey of 796 fertility centers worldwide showed that 51% of clinics considered AMH was the best test for measuring ovarian reserve, while 40% reported AFC was the best test and only 6% selected basal FSH. However, age was considered the best factor to predict pregnancy at 80% response rate, a small percentage selected AMH (4%) or AFC (3%).

Typically, an elevated FSH and low AMH level according to standard range based on age is diagnosed as DOR in women having regular periods.

Approximately 10% of women in an infertility clinic, totaling 275,000 women in the USA, are diagnosed with DOR. Recent CDC report from the USbased national Society for Assisted Reproductive Technology (SART) system show 32% of in vitro fertilization (IVF) cycles (approximately 66,000 cycles) carry a diagnosis of DOR2.

Facts to remember

  • Generally decreased AMH levels will present earlier than the rise in FSH in women. Therefore, if baseline FSH and estradiol levels alone were used for ovarian reserve testing and those levels are within normal ranges, a woman may be given false reassurance without knowing her AMH results, too. Ovarian reserves should always be measured in reference to entire battery of tests as mentioned above.
  • DOR is a normal physiologic process when it occurs in the mid-40s meaning women in 40’s are expected to run out of eggs and is a normal process of aging however it is pathologic at younger ages of 20s and 30s.
  • Younger women with DOR have a much greater chance of pregnancy with their own eggs compared to advanced age women.

 

POF/POA/POI vs DOR:

Approximately 1% women undergo Premature Ovarian Failure (POF) meaning women completely run out of eggs at younger age and undergo menopause. POF is characterized by postmenopausal levels of FSH (> 40 IU/L), four or more months of absence of periods, and age < 40 years.

POF, POI (Premature Ovarian Insufficiency) and Premature Ovarian Aging (POA) are often used interchangeably. The term POI was first introduced in 2007–2008 mostly due to the psychological impact associated with word “failure” on women hence a mild term Premature Ovarian Insufficiency was coined to better illustrate the condition.

POI women can occasionally start getting their periods randomly, they can be considered fertile during this period and may conceive naturally. However, they invariably have to resort to donor eggs if they wish to become pregnant.

 

POR vs. DOR:

DOR women when subject to conventional ovarian stimulation protocols tend to produce Poor Ovarian Response (POR) resulting in a reduced number of retrieved oocytes in IVF cycle.

The poor response in IVF is attributed to (i) advanced maternal age or any other risk factor for POR; (ii) a previous POR; and (iii) an abnormal ovarian reserve test (ORT). ESHRE (European society of human reproduction and embryology) introduced Bologna criteria to standardize the definition of POR based on key features of age, FSH, AMH, AFC and other risk factors. However, the discussion is still ongoing regarding cut-off levels for each of the categories to reach to more uniform definition of POR across various fertility clinics4.

POR is not only accompanied with DOR as there are many other conditions associated with poor ovarian response to stimulation regimens eg women with endometriosis or women with previous history of ovarian surgery for removal of ovarian cysts. Neither of these examples are considered a cause of DOR however they usually result in poor response to ovarian stimulation.

Resources:

  1. https://link.springer.com/article/10.1186/s12958-015-0026-z
  2. https://www.cdc.gov/art/pdf/2016-report/ART-2016-National-Summary-Report.pdf
  3. https://www.ncbi.nlm.nih.gov/pubmed/26347341
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650906/
  5. https://www.centerforhumanreprod.com/fertility/female-age-fertility-age-important-pregnancy-predictor/

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s