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Reproductive Aging. What is it?

For the past six months, H, 40, was puzzled as to why her menstrual cycles were getting very irregular, lasted for a shorter duration and the flow was less.

“My menses used to be very regular every month and lasted 6 days,” she recounted. “But now, I menstruate between 40 to 60 days and it lasts two days at the most. Am I having an early menopause?” she asked.

H had been married for 7 years. She had only tried to actively conceive the past 3 years as she thought that she could get pregnant anytime she wanted with the help of advanced reproductive technologies. However, with three failed attempts of IVF and two unsuccessful transfers of frozen embryos, she had become disillusioned, angry and depressed. With time, she eventually came to terms with her infertility.

She had a right dermoid cyst which was operated on when she was a teenager. At the age of 28, she was diagnosed with endometriosis and had a chocolate cyst removed from her left ovary.

Her blood level of the pituitary follicular stimulating hormone (FSH) was slightly elevated and the Anti-Mullerian hormone (AMH) was low for her age. Ultrasound pelvic examination revealed that her ovaries had a reduced number of follicles. H was suffering from reproductive aging.

What is reproductive aging (RA)?

Reproductive aging refers to the functional decline of the female reproductive system due to tissue and cell deterioration. It is a natural process that occurs in all women, eventually leading to reproductive agedness and menopause. With the increasing trend of late marriage and delayed motherhood, many women like H, often misjudge the age at which a significant decline in fertility occurs and overestimate the success of assisted reproductive technologies to circumvent infertility.

What are the causes of RA?

  1. Age: Women are born with a finite number of eggs during foetal development. Eggs peak in number when the foetus is about 20-week-old with approximately 6-7 million eggs. They then undergo degeneration, and do not regenerate. At birth, the number of eggs falls to 1-2 million, and at puberty, only 300,000-500,000 eggs are left. From puberty through menopause, women release one egg per month. It is estimated women will ovulate about 400-500 eggs in their reproductive life. After menopause, the ovary no longer releases eggs. Besides quantity, the quality of the eggs also deteriorates with age. It is optimal when the woman is in her mid-20s, representing the most fertile period in her life. After 35, there is a significant decline of fertility potential, with further deterioration after 40s.

  2. Smoking: Cigarette smoke contains a mix of over 7,000 chemicals. Many of these chemicals such as carbon monoxide and nicotine can damage the ovarian cells. Studies have shown that smokers will have a menopause two years earlier than the non-smokers.

  3. Surgery: Surgical removal of ovarian cysts will invariably damage the surrounding healthy tissue. Should complications arise occasionally, the gynaecologist may have no choice but to remove the entire ovary. In both situations, ovarian reserve will be reduced.

  4. Ovarian diseases: Endometriosis, pelvic inflammatory disease and ovarian cancer can cause damage to the ovary.

  5. Radiation, chemotherapy and drugs: Low ovarian reserve can result from these agents.

  6. Genetic diseases : Some rare genetic conditions can cause premature aging of the ovary.

What are the consequences of RA?

RA can result in increased incidence of

  1. Infertility

  2. Miscarriages, stillbirth, prematurity and Cesarean section

  3. Failure rate of IVF and other assisted reproductive technologies

  4. Early menopause

How is RA diagnosed?

RA is usually diagnosed by the assessment on day 2 or 3 of the menstrual cycle of serum FSH (follicle-stimulating hormone) and oestrogen level, AMH (anti-Müllerian hormone), and the ultrasound examination of the ovary (Antral follicle count).

However, the results should be interpreted with caution as they are not strictly accurate in predicting the pregnancy potential and the age of menopause.

When H was first told of her diagnosis, she was in a state of disbelief. But when symptoms of early menopause started to appear one year later, she gradually accepted her condition. With the support of her husband, H now gracefully awaits the arrival of menopause.

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