Aging and infertility


Aging and infertility:
The process of aging affects all biologic system
Women have a short reproductive life and fertility potential begins to decline in the mid thirties- 10 years before menstrual irregularities appear.
Reproductive potential decline along with age due to
1. Intrinsic aging of the reproductive system
2.  Weathering-which refers to the increase with age of certain conditions that influence
the reproductive system.

Factors those affect fertility in women

  • Endometriosis
  • Pelvic infection
  • Systemic infection
  • Smoking
  • Diabetes
  • Myoma
  • Adenomyoma
  • Hypertension and obesity

In men an example of such a problem is

  • Impotence (Incapable to perform intercourse), which can be influenced by
    • Diabetes
    • Therapy for hypertension
    • Impaired cardiac function

Socioeconomic factors influence the fertility potential of women like poor nutrition, poor health, promiscuity (multiple sexual partner) and pelvic infection.
In modern society
Delay in marriage and child bearing (Carrier development) and changing sexual practice like widely used contraception and more sexual partners affect fertility.

Fertility rates in different ages:
Fertility rates drops along with increasing age

25-29  yrs

4%—8% drop

30-34  yrs

15%—19% drop

35-39 yrs

26%—46% drop

≥ 40 yrs

60%—70% drop

≥ 45 yrs

92%      drop

Effect of age in the component of female
There is evidently a decrease in fertility rate with age .Main reason for decrased fertility appears to be decreased ovarian function and oocyte quality. Ovarian function is characterized by the quantity and quality of oocyte released and the hormonal mileeu of the preovulatory follicle and post ovulatory corpus luteum and its progesterone production. Oocyte reservoir, oocyte quality and ovarian responsiveness to gonadotropins may decline with advancing age. Menstrual cycle also becomes shorter and irregular 3-9 yrs before onset of menopause. Decrease in ovarian function and its reserve with age is progressive and subtle.

Follicular dynamics and oocyte depletion:
There are 7 million oocytes at 7th month of intrauterine life, which reduced to 2 million at birth and 400000 by the time of first menstruation (menarche). This occurs because oocytes undergo continuous apoptosis (programmed cell death) and atresia. This depletion is an ongoing process from birth till menopause and beyond and there is no method by which oocyte depletion can be delayed. This constant and dynamic process of decline continues until menopause, and is not interrupted by birth control pills, pregnancy, or ovulation. From this reservoir of eggs, fewer than 500 eggs will ovulate during a woman’s reproductive years, and the rest will undergo a degenerative process entitled “atresia”. Smoking appears to accelerate atresia, and is linked to earlier menopause.

In some situation depletion may be faster which are

  1. Genetic:  X chromosomal microdeletion
  2. Family history
  3. Poor nutrition
  4. Smoking
  5. Gonadal dysgenesis ( Birth defect)
  6. Mumps
  7. Oophorities
  8. Autoimmune disease
  9. Chemotherapy
  10. Radiotherapy

Ovarian reserve:
It is the estimation of number of oocytes in the womens’ ovary.
Ovarian reserve is declined due to

  1. Aging
  2. Faster depletion
  3. Endometriosis
  4. PID (Pelvic inflammatory diseases)
  5. Repeated pelvic surgery

Assessment of ovarian reserve:
Ovarian reserve can be assessed by measuring serum FSH and E2 on D1-D3 of menstrual cycle. Number of antral follicle in early follicular phase is also a predictor of ovarian reserve. Optimum reserve is predicted if values are like this
D1-D3 FSH: < 10 IU/L and E2: < 100pg/ml
Antral follicle count: 7mm, 8-10 follicle

Other  parameters for ovarian reserve assessment are
Inhibin B: 180 pg/ml or more
AMH : >1ng/ml
CCCT (clomiphene citrate challenge test):   FSH<20 on D10
GnRH agonist stimulation test: 100 pg/ml or more
It is customary to inform the patient that if, during the early phase of a natural cycle, the FSH is >19 mIU/ml, the possibility of pregnancy occurring is almost nonexistent. By the time the woman reaches menopause at about age 48-53, the ovaries will contain few or no eggs.

Female age is extremely important when considering the probability of pregnancy. The real issue is egg quantity and quality, which then converts to embryo quality after fertilization. Increased infertility with age is a well-documented problem and most apparent in modern society.
Successful pregnancy outcome with treatment is largely related to female age, particularly when using the woman’s own eggs.

Changes in quality of oocyte
Quality of eggs reduced along with age due to prolonged arrest in dictytene stage, prolonged exposure to environmental toxicants which cause mutation. As a result there is less fertilization and implantation. The relationship between the age of the female partner and fertility. The study found that the percentages of infertile couples were:

•    By age 30 =  7%
•    By age 35 = 11%
•    By age 40 = 33%
•    At age 45 = 87%

In a review of data from the various IVF centers in the USA, the Central for Disease Control  reported that the live birth rate was 16% per cycle at age 40, and only 3% per cycle at age 44.

Miscarriage and female age

Numerous studies have documented the increased risk for miscarriage as the age of women advances.. Miscarriage is defined as spontaneous pregnancy loss before the 20th week of gestation.

Miscarriage rates for women with a history of infertility tend to be higher than for those who are fertile. Most of the increased risk for miscarriage in “older” women is due to the rise in chromosomal abnormalities (karyotype) in their eggs. However, this is still a controversial issue, as not all published data are in agreement.
Miscarriage rates begin to increase among women in their mid-to-late thirties, and continue with advancing age, reaching 43% at age 42 years. The miscarriage rates observed among women undergoing assisted reproductive technology (ART, i.e. IVF) procedures appear to be no higher than those pregnancies conceived through intercourse.
The miscarriage rate after fetal heart activity seen on ultrasound was 11%, 20% and 41% at ages 30, 38, and 42 years of age, respectively.

Chromosomal problems in aging eggs

We are not fully aware of why, as women age, chromosomal abnormalities are higher in eggs. However, research studies have clarified some of the issues involved.
The meiotic spindle is a critical component of eggs, with involvement in organizing the chromosomal pairs so that proper division of the pairs can occur as the egg develops. Ultimately, it appears that as women mature, the incidence of chromosomally-abnormal eggs increases dramatically. This results in lower chances for conception, as well as increased risk for miscarriage.

Risk of Chromosomal Abnormality in Newborns by Maternal Age

Effect of age on male infertility

Decline started at 40. There is age related decrease in spermatogenesis, total sperm count and sperm motility and morphology.
The age of the male partner is not quite as important. This is due to the fact that all the female eggs are present at birth, whereas sperm are generated constantly after puberty. Eggs age over time, while new sperm continue to appear from the production line.