2. Laboratory Challenges of Female Infertility Diagnosis - Part II (Ovarian Follicles)

2. Laboratory Challenges of Female Infertility Diagnosis - Part II (Ovarian Follicles)

Ovarian follicle structure?

Ovaries are actually immature primary oocytes that are surrounded by a cellular structure called the primordial follicle. .

The follicle is a structure that forms part of the ovaries, and the ovum (also called the oocyte, or immature ovum) is a cell that is arranged regularly from the inner wall of the follicle in the adult menstrual cycle. And is released. .

• Primary eggs are formed in the embryonic period between 10 and 30 weeks, and their number reaches 6-7 million, and then decreases. Every baby girl is born with one million to one million two hundred thousand oocytes at birth. .

• This decrease continues and reaches 300 to 500 thousand at the beginning of puberty. .

• There are many differences between different women in terms of quantity and quality of egg storage, ovarian reservation and the time of occurrence of reproductive events such as puberty and menopause. .

In addition to environmental, social, economic, behavioral, and anatomical problems, genetic issues also affect a person's fertility. .


• There are hypotheses about the association of certain genes, including BRCA1‌ mutations, and reduced ovarian reservation, which need further investigation.

• Smoking is a harmful habit that has been shown to reduce ovarian reserve, but reducing ovarian reserve markers does not always occur.

• Over time, ovarian function changes. During puberty, when ovulation and menstruation begin, one egg develops each month and is released from one of the ovaries.

In addition to the egg, the follicle has other cells that release the estrogen needed to mature the egg, called granuloma cells, and their number increases under the control of blood gonadotropins and decreases under the control of blood testosterone. .

• Primary follicles contain only one layer of broad granuloma cells and are about 0.03 to 0.05 mm in diameter. These cells can remain in the ovaries for up to 50 years.

• Primary follicles (which contain cubic granulosa cells and are about 0.1 mm in diameter) originate from primary (primordial) follicles, which undergo changes in both histological and hormonal changes to the primary follicle. Granulose cells are transformed from a wide state to a cubic cell.

These cells display FSH receptors on their surface but are not dependent on gonadotropins until they are converted to antral follicles (although in vitro studies show that FSH facilitates follicular growth. And the stimulation of the primary follicles begins).

In the primary follicles, a polymeric capsule layer of glycoprotein called zona pellucida forms around the oocyte, which accompanies it even after ovulation and contains enzymes that help sperm to penetrate the egg. Does.

• These follicles then turn into secondary follicles (which contain several layers of granulosa cells and Teka cells are seen at this stage and are about 0.2 mm in diameter).

 In this follicle, two layers of internal and external Tak cells are formed, between which they are filled with a network of layered capillary vessels.

• Secondary follicles also become tertiary or antral follicles in the process of subsequent changes.


• The third follicle is classified into different categories based on size, ranging in size from 0.2 to 5 mm.

By day 4 to 6 of the menstrual cycle, only one of the third follicles remains and continues to grow until day 13 of the cycle, reaching its 8th growth rate (diameter about 20 mm) and the rest of the follicles in Growth is now analyzed (this process is called atresia). .


Granulose cells Antral follicles have very sensitive receptors to gonadotropins (especially FSH), which increase the production of estrogen by these cells. Both estrogen and FSH are important in accelerating the growth process of antral follicles.

• Antral follicles can be detected on ultrasound and one of the criteria for determining ovarian reserve is counting these follicles on the third day of menstruation.

• At this stage, Teka cells show LH receptors on their surface and under the influence of this hormone, androgen production - especially androstenedione - is increased, and these hormones are aromatized in granulosa cells and converted to estrogen (especially estradiol). ) be.

Thus, a sharp increase in estrogen levels is caused by tertiary follicles. In other words, LH increases the production of androgens in Teka cells, which in turn increases estrogen levels.

• Granulose cells produce a series of peptide hormones that belong to the Transforming Growth Factor (TGF) / activin family, which include: Relaxin, inhibin A, inhibin B, activin, follistatin. And AMH.

• The role of activin is to proliferate granulosa cells, regulate the expression of FSH and LH receptors, increase the release of gonadotropins by affecting the hypothalamus and pituitary gland, increase the activity of the aromatase enzyme to convert androgens into estrogens in cells. Granuloma,

 It inhibits the production of androgens, increases the production of inhibin and folliastatin, and ultimately intensifies the growth phase of oocytes.

• There are two types of inhibin compounds. Inhibin A consists of two subunits of alpha and beta-A and inhibin B consists of two subunits of alpha and beta-B. Both inhibit FSH secretion from adenohypophysis. .

• The inhibin A molecule is also secreted by the corpus luteum. In the initial stage of the follicular phase, the level of inhibin A is slightly secreted, and then in the final stage, the follicular phase increases and reaches its peak in the mid-luteal phase. .

• Inhibin B production is increased by granulosa cells of tertiary follicles and, along with increased estradiol, has a inhibitory effect on FSH production at the end of the follicular phase. Its level reaches its maximum during ovulation. Inhibin B also affects Taka cells and increases the production of androgens.

The AMH که hormone, which is produced by granulosa cells of the antral and small antral follicles, is activated by inhibiting the extreme mobilization of follicular growth, which is increasing cyclically and stimulated by FSH. It prevents a large number of primary follicles and therefore plays an important role in folliculogenesis.

The level of this hormone appears to reflect the growth rate of non-FSH dependent follicles. When the follicle undergoes its FSH-dependent developmental stages and matures, the production of this hormone is stopped.

• So far, the oocytes have been in the early stages and have stopped in the phase phase of meiosis I. During the pre-ovulation phase, meiosis continues and stops in the secondary oocyte stage, which includes the metaphase II stage. .

• On days 12 to 13 of the cycle, the production of luteinizing stimulating hormone (LH) peak (called LH Surge), which converts the antral follicle into the dominant follicle, which is the same stage. The end of the follicle is the third, and it is called the pre-ovulatory follicle (‌ The late tertiary or pre-ovulatory follicle).

 It contains a fluid-filled cavity (antrum) called the Graafian follicle, which ruptures in the next 24 to 36 hours as the FSH increases and releases secondary oocytes. Does.

In other words, LH is responsible for the final maturation of follicles and oocytes.

• The whole process of folliculogenesis takes 375 days, ie from the time of group awakening of the primary follicle to the occurrence of ovulation, it takes 375 days, and the initial follicle that awakens in one cycle in its 13th cycle. It is either converted to the dominant follicle or underwent apoptosis and degeneration.

It takes a day to convert an awakened primary follicle to a secondary 290 (pre-antral follicle). During this time, primary and secondary follicles are neither sensitive to gonadotropins nor produce AMH.

• It takes 50 days for the third follicle to become the dominant follicle.

• From the beginning of growth and stimulation of secondary follicles (antral follicles) until the antral follicle reaches a diameter of about 2 to 6 mm, the hormone AMH is produced by granulosa cells, the amount of which depends on the number of small antral follicles. (The amount of these follicles also depends on the amount of storage of the primary ovarian follicles).

Each month, 500 or more eggs are broken down inside the ovary and never grow or are released for possible fertilization.

• In a regular cycle, different follicles become large and mature, but only one follicle can complete the maturation process each month. .

• Note that the process of folliculogenesis is a continuous process and different follicular stages are seen in the ovaries at each moment. .

In each cycle, the egg is randomly released from one ovary, and sometimes both ovaries ovulate together.

Loss of 500 eggs this month means that women's ovarian reserves are declining dramatically.

• Even if the egg reserves are depleted, there is still an egg. Therefore, they can be stimulated with drug therapy to grow and get rid of the ovaries. This is called "ovulation induction."

• By the end of childbearing age, a relatively small number of eggs usually remain at the age of 45, many of which have genetic disorders.

• Ovarian storage in postmenopausal women reaches about 1,000.


Therefore, in the total active period of a woman's sexual activity, only about 400 follicles reach their final stage of development and release the egg.

RelatedNews 2. Laboratory Challenges of Female Infertility Diagnosis - Part II (Ovarian Follicles)

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