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In Vitro Fertilization (IVF) The Good, The Bad, And The Ugly

The American Society of Reproductive Medicine (ASRM) defines infertility as the failure to achieve a successful pregnancy after 12 months or more of regular unprotected intercourse. Earlier evaluation and treatment may be justified based on medical history and physical findings and is warranted after 6 months for women over age 35 years. In the United States one in six couples are infertile. In large urban areas where women often delay childbearing for sake of their career, the proportion can be as high as one in five. This high incidence is confirmed by the oft-quoted statistic that in the United States over 3 million women a year visit a physician because of difficulty in conceiving. To put things in perspective however, male factor infertility is the sole cause of infertility in approximately 20% of infertile couples, and is a contributing factor in another 30% to 40%.

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Unlike men who continue to produce sperm throughout their lives, women are born with their full complement of eggs (oocytes, ovum), normally in excess of 1 million egg bearing ovarian follicles. At the onset of puberty the number of eggs has been reduced to 300,000 to 500,000 and during the next 35 to 40 years of reproductive life a women will ovulate (release and egg) 400 to 500 times and the rest of the follicles will undergo atresia. Atresia refers to the hormonally regulated degeneration and subsequent resorption of one or more immature ovarian follicles. Atresia is a process that continues through a women's reproductive life regardless of whether a women has regular menstrual cycles, is pregnant or uses birth control. The egg bearing follicles will ultimately be depleted to a point at menopause that only a few hundred remain.

During the reproductive years most women ovulate monthly. If the egg is fertilized and implants in the endometrium, the liming of the uterus, pregnancy ensues. If fertilization and implantation do not occur the hormone thickened endometrium will be sloughed off in the form of menstrual flow.

Physiology

The reproductive (menstrual) cycle refers to the maturing and release of an egg and to the preparation of the uterus to receive and nurture and embryo.

The cycle is controlled by the hypothalamus in the brain. Neurosecretory cells in the hypothalamus produce the gonadotropin-releasing hormone (GnRH) that acts on the cells of the pituitary gland which in turn secrete gonadotropins, FSH & LH. FSH is the follicle-stimulating hormone - LH is the luteinizing hormone. Both FSH & LH stimulate and control cyclic changes in the ovary (ovarian cycle). The hormones estrogens and progesterone are produced by the ovaries under the influence of FSH and LH and simultaneously promote the cyclic changes in the structure and function of the endometrium, the lining of the uterus, (menstrual cycle). Thus, the cyclical activity of the ovaries is intimately timed with changes in the uterus so that after fertilization of the egg occurs, the endometrium is prepared for the implantation of an embryo. Development of the follicle bearing egg, fertilization, and implantation of the fertilized egg in the receptive endometrium, must be exactly timed or pregnancy will not occur.

The reproductive cycle generally lasts 28 to 32days and is divided into three distinct phases: the follicular phase, the ovulatory phase and the luteal phase.

The follicular phase, which begins on the first day of menses lasts approximately 10 to 14 days and is the period the egg-bearing follicles grow and develop. GnRH released by the hypothalamus signals the pituitary gland to release FSH, which in turn stimulates the growth of several ovarian follicles. One follicle, in one of the two ovaries, will be selected to be the dominant follicle and it's egg will selectively mature. The other follicles will undergo atresia and be resorbed. As the dominant follicle increase in size it releases increasing amounts of estrogen in to the bloodstream creating a feedback that signals the hypothalamus and pituitary to reduce the production of FSH. The dominant follicle, also known then as the graafian follicle, ultimately reaches a diameter of up to 25 mm. Around day 14 the proliferative phase ends with the LH surge.

In the early follicular phase, after menstrual flow has ended, the lining of the uterus is at it thinnest. Levels of estrogen are at their lowest. Later in the follicular phase, as estrogen rises proliferation (or thickening) of the uterine lining (endometrium) occurs. This thickened lining is preparing for a possible pregnancy.

The ovulatory phase begins with the LH surge and ends approximately 36 hours later with ovulation. Ovulation is the release of the egg from the dominant follicle into the fallopian tube, where it awaits fertilization by the partner's sperm. As the dominant follicle grows toward the end of the proliferative phase increasing amounts of estrogen trigger the pituitary gland to release a surge of luteinizing hormone, LH. Detection of LH in the urine is the basis of ovulation prediction kits and indicates that ovulation will occurs within the next 36 hours. An egg lives 12-24 hours after leaving the ovary so intercourse must occur prior to or at ovulation if pregnancy is to occur. Sperm can wait for the egg but the egg cannot wait for sperm. Among healthy women trying to conceive, nearly all pregnancies can be attributed to intercourse during a six-day period ending on the day of ovulation. Sperm that have entered the cervical mucus are nourished there and can survive for long periods, certainly, for several days after intercourse. Once in the cervical mucus, they are stored in the crypts and are propelled upwards, in waves from the cervix to the uterus and fallopian tubes, over a period of 48 to 72 hours. Thus, the cervical mucus acts as a sperm reservoir.

The luteal phase begins at ovulation and lasts for 14 days. After the egg has been released from the dominant follicle it closes and this empty sac becomes known as the corpus luteum. The former dominant follicle accumulates a yellowish pigment, lutein, that lends it's name to the process of luteinization and the corpus luteum. In the 14 days of corpus luteal life, which is dependent on low but continuous quantities of LH being available, the corpus luteum secretes the hormones progesterone, androgens, and estrogens. Secretion of large quantities of progesterone marks the luteal phase. By day 8 or 9 after ovulation, peak development of the corpus luteum occurs, and peak levels of progesterone and estradiol are seen. Progesterone causes the lining of the uterus, the endometrium, to enter the progestational (or secretory phase) in preparation for implantation of an embryo.

If the egg (oocyte) is fertilized and implantation occurs, degeneration of the corpus luteum is prevented by the emergence of a new stimulus, human chorionic gonadotropin (hCG), an LH-like hormone produced by the developing embryo and secreted into the maternal blood stream. A rapidly rising hCG is the sign of a healthy pregnancy. Since implantation in the endometrium normally occurs about 6-7 days after ovulation, hCG stimulus must appear at the peak of corpus luteum development (by the 10th day after ovulation), just in time to rescue the corpus luteum and prevent luteal regression. hCG, produced by the embryo and secreted into the maternal bloodstream is the substance that is detected in pregnancy tests.

In early pregnancy, hCG maintains the vital steroidogenesis (production of sex hormones) of the corpus luteum until approximately the 10th week of gestation, by which time secretion of progesterone and estrogen by the placenta becomes adequate for maintenance of pregnancy. The corpus luteum regresses slowly after the 10th week of pregnancy.

Fertilization and Pregnancy:

After traversing the cervix and reaching the fallopian tube sperm can fertilize an egg. Fertilization is the process by which male and female gametes fuse to form the zygote (a unicellular embryo). Fertilization usually takes place in the ampulla, the widest part of the fallopian tube, 12 to 24 hours after ovulation. After this period of time, the egg loses it's ability to be fertilized and begins to degenerate. If fertilized, the resulting embryo reaches the uterus about 3-4 days later in the morula stage (12 to 16cells) and implants in the endometrium on the 6th or 7th day as a blastocyst (pregnancy).

If fertilization does not occur degeneration of the corpus luteum is inevitable. Failing an increasing source of hCG from a successful implantation, the corpus luteum rapidly declines 9-11 days after ovulation. Its vascularity and lipid content wane, it begins to shrink and degenerate. Simultaneously, progesterone production decreases, precipitating menstrual bleeding by the shedding of the compact and spongy layers of the endometrium. The luteal phase of the cycle is thus regulated by the limited 14-day functional lifetime of the corpus luteum. The entire system then resets and a new cycle begins.

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Posted in Food Post Date 03/12/2017


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