Evaluation

In order to find the cause of infertility, it is important to understand what happens during a typical natural ovarian cycle. Below is a simplified summary of the steps required for natural conception to occur.

  1. Recruitment phase (cycle day 1-4)- during this period the pituitary sends out Follicle Stimulating Hormone (FSH) to recruit as many eggs as the ovaries can afford to give in a cycle. The available number of eggs depends on the woman’s age and egg reserve.
  2. Selection phase (day 5-9)- Many eggs are then eliminated through a natural selection process as the FSH signal decreases
  3. Dominance phase (day 10-13): From the selected eggs only one will be allowed to continue grow and mature. This is Nature’s way of ensuring that only one baby is conceived at a time. The one remaining egg resides in fluid filled sac called a follicle. At full maturity the dominant follicle is about the size of a grape (2 cm). Lining the inner surface of the follicle are the granulosa cells, which act as supporting cells to promote the growth and development of the egg. These cells proliferate under the FSH signal and produce estrogen which is important in the development of the egg and the uterine lining. They are the same cells that will produce progesterone to prepare the endometrium for implantation.
  4. The LH surge (~day 13-16): Once the dominant follicle reaches at least 18 mm, it has an egg ready to be released. The brain sends signal to the pituitary to release a spike of luteinizing hormone (LH). LH has 4 main effects on the mature follicle:
    • LH instructs the egg to undergo changes that allows it to become fertilizable by the sperm to create an embryo.
    • LH allows the egg to detach itself from the wall of the follicle to enable it to escape after ovulation.
    • LH acts on the granulosa cells that line the interior of the follicle to make them start producing progesterone to prepare the uterine lining (the follicle is now called the corpus luteum)
    • Finally, LH initiates a cascade of events to weaken and break down the wall of the follicle to make an exit point for the now fully mature egg.
  5. After ovulation, the egg is dropped into the pelvic space. The posterior cul de sac is the region behind the uterus that is also the lowest internal space of the upper body in standing or lying position. In this space the egg resides for several hours, in a small pool of fluid, before it is picked up by either fallopian tube. Unfortunately, the posterior cul de sac can also be the region where menstrual blood, endometriosis, purulent materials from past pelvic infection, and fibrin exudates from prior abdominal surgeries can accumulate. With time, these materials can become adhesions and scarring, creating pockets that can make it difficult for the egg to be found.
  6. Egg pickup- the egg is viable for only 24 hours after ovulation, so it is critical that it has a chance to be fertilized as soon as possible. The distal region of the tube (the fimbriae) is the widest region and most important part of the tube. It acts as a catching glove to pick up the egg and also as an initial fertilizing chamber where the egg and the sperm meet. Any damage to the fimbriae will significantly reduce the chance of pregnancy.
  7. Fertilization (~day 13-16) – The egg must be fertilized within 24 hours after ovulation in order for an embryo to form. While only one sperm is needed to fertilize the egg, enough sperm must be within the vicinity of the egg for this to occur. Experience with in vitro fertilization has shown that at least 50,000 motile sperm must be near an egg for successful fertilization. Ideally, only one sperm should penetrate the egg; however, there are also the possibilities that none get in, or multiple sperm enter and cause abnormal fertilization.
  8. Tubal transport (~day 14-20)- As the newly fertilized egg travels through the length of the tube over the next 5-6 days, it actively undergoes cell division and development to become a blastocyst when it reaches the uterine cavity. It is during this period that many human embryos stop dividing due to chromosomal abnormality. The division process can result in an abnormal embryo that becomes nonviable by the time it reaches the uterus. It has been estimated that only 20% of embryos will survive the trip through the tube. Good egg quality is required for normal embryo development and survival of the embryo.
  9. Implantation (~ day 20-22)- This is the critical step. The embryo, now fully mature, escapes from its protective shell (zona pellucida) and finds a spot in the uterus to attach to. For the previous week, after ovulation, the granulosa cells of the dominant follicle had been producing progesterone to induce drastic changes of the endometrial glands and vascular network within the uterine lining. Nutrients, growth factors, and other ingredients critical for implantation were brought into the endometrium. Progesterone is essential for the implantation and maintenance of a pregnancy. Known causes of implantation failure include inadequate progesterone action, embryo nonviability, infection, structural abnormalities (polyp, tumor, septum), and thin endometrium (< 6 mm). Unfortunately, the causes for many cases of implantation failure remain unknown.
  10. Early pregnancy- Once implantation occurs, the cells from the embryo start to produce human chorionic gonadotropin (HCG) to maintain progesterone production from the corpus luteum to support the pregnancy. HCG can be detected by a blood or urine test a week after implantation (or on the first day of missed menses).

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