BRUCE I. ROSE, PhD, MD
SAMUEL BROWN, MD
Everyone knows that a man and a woman produce a baby using their eggs and sperm. This is a miraculous process shrouded in mystery and hope. Contemporary infertility care enables doctors to help couples conceive a child even when things are less than optimal. Our tools and techniques have grown out of our understanding of this physiological process after more than 30 years of performing in vitro fertilization (IVF). What follows is an attempt share some of the complexity underlying this process that so affects us all.
All of the eggs that a woman ovulates in her lifetime were created as primordial follicles when she was a fetus. Each primordial egg has a single layer of specialized granulosa cells surrounding it. These cells play an important role in the future development of that egg. A woman's body releases these eggs from their arrested state slowly over the course of the woman's reproductive life. The process that triggers an individual egg's release is not understood, but intra-ovarian androgens are likely a contributing factor.
At birth, women start life with about a million primordial eggs. Women release eggs from their arrested state during their childhood and during all stages of their growth and development. During a woman's peak reproductive years (age 18-30), about 1000 eggs are released each month. Intra-ovarian growth factors and hormones cause some of these eggs to grow in the ovary for about five months. Most of the eggs that were released will wither away (apoptosis). During this time period, the egg increases its volume approximately 4-fold. Most of the volume increase is due to an increase in the number of energy producing mitrochondria. The granulosa cells that surrounded the primordial egg become multi-layered and differentiate into two types of cells which nurture the developing egg and produce estrogen to prepare the lining of the uterus for implantation. During this time period, the egg secretes a shell (zona pellucida), which plays an important role at the time of sperm penetration into the egg.
After about five months, fluid secretions from the granulosa cells begin to collect in a small sac surrounding the egg and some granulosa cells (follicle wall). When this cyst is 6 mm in diameter, the granulosa cells begin to develop receptors for FSH. This initiates exponential growth driven by the hormone FSH and augmented by the estradiol produced. Granulosa cells and the egg work together to supply the eggs with the molecular products it needs to prepare for ovulation, fertilization and early embryo development. Fifty million granulosa cells are now contained in the follicle. When the follicular cyst has a diameter of 18-20 mm, egg is ready to leave the ovary.
The estradiol produced by granulosa cells has also been acting on the pituitary to produce a trigger for ovulation: the release of a spike of LH. LH triggers ovulation in part by inducing collaginase production in the follicle which breaks down the follicle wall and frees the oocyte from its attachment to it. The egg contains four times too many chromosomes and LH causes changes with the egg that enable completion of the first meiotic division in which one-half of the chromosomes are pushed out of the egg (first polar body) in preparation for sperm penetration.
In the natural cycle, as a woman moves around during her day, the tubes and ovaries move around in her body and the delicate ends of the tube locate the egg and move it inside. Sperm from intercourse has colonized the crypts within the cervix. As they swim out, a few will reach the end of the tube and find the egg.
Most sperm are not capable of fertilizing an egg even if they are lucky enough to find one. Those that can, will tightly attach to the zona pellucida composed of three proteins surrounding the egg. It takes sperm about two hours to penetrate this protective shell. After binding to the shell, the pattern of sperm tail movement changes, in part, beating more vigorously. Binding to the zona pellucida prevents a sperm from bouncing off as it tries to penetrate the shell. Motility changes convert the business of the sperm from finding the egg to directing their force into penetrating it. The head of the sperm contains a sac of digestive enzymes (acrosome). After binding to the zona pellicida, the sac fenestrates and leaks the enzymes into the zona to facilitate passage of the sperm into the eggs.
As the first sperm that passes through the zona, the head is taken into the egg and fuses with the egg cell membrane. This induces a secretory reaction which causes the zona pellucida to harden and prevent further sperm penetration. If two sperm enter the egg before this reaction can take place, the resulting cell is not compatible with becoming life. The sperm's entry into the egg causes the egg to reduce its chromosomes to the desired number as it produces a second polar body. The sperm head rearranges its chromosomes and becomes the male pronucleus which matches up with a similarly constructed female pronucleus. These structures fuse and we have a cell with the correct number of chromosomes. There are many more hurtles for this complex cell to overcome to become a baby. The early embryo will not implant into the uterus for seven days. It has stored all of the energy required to support its rapid cell division in preparation for implantation. These include the inherited components from the particular egg and sperm starting this journey and the environment in which this fertilized egg finds itself.
The reproductive process can go wrong at many levels. As our understanding of the process of reproduction increases, we are able to diagnose and bypass these problems. Almost all couples have the potential to become parents using contemporary tools.
Founded by Dr. Samuel E. Brown, Brown Fertility offers a fully comprehensive array of fertility treatments, including in vitro fertilization, egg donation and artificial insemination and is home to Florida's most state-of-the-art IVF center, which produces some of the highest pregnancy rates in the country. With over 80 years' experience, and the management of more than 7,000 IVF cycles, the providers at Brown Fertility have earned a reputation for not only producing excellent outcomes and offering affordable treatment options, but also for providing patients with the one-on-one attention and the compassionate care they deserve. Visit www.BrownFertility.com for more information.