Fertilization occurs when a sperm and an oocyte (egg) combine and their nuclei fuse. Because each of these reproductive cells is a haploid cell containing half of the genetic material needed to form a human being, their combination forms a diploid cell. This new single cell, called a zygote, contains all of the genetic material needed to form a human—half from the mother and half from the father.

Overview

Hundreds of millions of sperm deposited in the vagina travel toward the oocyte, but only a few hundred actually reach it. The number of sperm that reach the oocyte is greatly reduced because of conditions within the female reproductive tract. Many sperm are overcome by the acidity of the vagina, others are blocked by mucus in the cervix, whereas others are attacked by phagocytic leukocytes in the uterus. Those sperm that do survive undergo a change in response to those conditions. They go through the process of capacitation, which improves their motility and alters the membrane surrounding the acrosome, the cap-like structure in the head of a sperm that contains the digestive enzymes needed for it to attach to and penetrate the oocyte.

The oocyte that is released by ovulation is protected by a thick outer layer of granulosa cells known as the corona radiata and by the zona pellucida, a thick glycoprotein membrane that lies just outside the oocyte’s plasma membrane. When capacitated sperm make contact with the oocyte, they release the digestive enzymes in the acrosome (the acrosomal reaction) and are thus able to attach to the oocyte and burrow through to the oocyte’s zona pellucida. One of the sperm will then break through to the oocyte’s plasma membrane and release its haploid nucleus into the oocyte. The oocyte’s membrane structure changes in response (cortical reaction), preventing any further penetration by another sperm and forming a fertilization membrane. Fertilization is complete upon unification of the haploid nuclei of the two gametes, producing a diploid zygote.

A man provides a semen sample. If the sperm are healthy, they are centrifuged to concentrate them and reduce the volume, placed in a dish with the egg, and left overnight in an incubator. Fertilization usually occurs on its own. However, sometimes sperm are not able to fertilize the egg on their own. When this is the case, a single sperm is injected into an egg using a needle. This process is called intracytoplasmic (pronounced IN-truh-sahy-tuh-PLAZ-mick) sperm injection (ICSI). About 60% of IVF in the Unites States is performed with ICSI. The pregnancy rate is about the same for IVF using natural fertilization or ICSI.

If sperm cannot fertilize the egg without assistance, couples should consider genetic testing. This testing can determine whether the sperm have chromosome problems that might cause development problems in the resulting embryos.

Embryos that develop from IVF are placed into the uterus 1 to 6 days after retrieval.

IVF, which stands for in vitro fertilization, is an assisted reproductive technology. In vitro, which in Latin translates to “in glass,” refers to a procedure that takes place outside of the body. There are many different indications for IVF. For example, a woman may produce normal eggs, but the eggs cannot reach the uterus because the uterine tubes are blocked or otherwise compromised. A man may have a low sperm count, low sperm motility, sperm with an unusually high percentage of morphological abnormalities, or sperm that are incapable of penetrating the zona pellucida of an egg.

A typical IVF procedure begins with egg collection. A normal ovulation cycle produces only one oocyte, but the number can be boosted significantly (to 10–20 oocytes) by administering a short course of gonadotropins. The course begins with follicle-stimulating hormone (FSH) analogs, which support the development of multiple follicles, and ends with a luteinizing hormone (LH) analog that triggers ovulation. Right before the ova would be released from the ovary, they are harvested using ultrasound-guided oocyte retrieval. In this procedure, ultrasound allows a physician to visualize mature follicles. The ova are aspirated (sucked out) using a syringe.

In parallel, sperm are obtained from the male partner or from a sperm bank. The sperm are prepared by washing to remove seminal fluid because seminal fluid contains a peptide, FPP (or, fertilization promoting peptide), that—in high concentrations—prevents capacitation of the sperm. The sperm sample is also concentrated, to increase the sperm count per milliliter.

The embryos are then incubated until they either reach the eight-cell stage or the blastocyst stage. In the United States, fertilized eggs are typically cultured to the blastocyst stage because this results in a higher pregnancy rate. Finally, the embryos are transferred to a woman’s uterus using a plastic catheter (tube). The figure below illustrates the steps involved in IVF.

IVF is a relatively new and still evolving technology, and until recently it was necessary to transfer multiple embryos to achieve a good chance of a pregnancy. Today, however, transferred embryos are much more likely to implant successfully, so countries that regulate the IVF industry cap the number of embryos that can be transferred per cycle at two. This reduces the risk of multiple-birth pregnancies.

The rate of success for IVF is correlated with a woman’s age. More than 40 percent of women under 35 succeed in giving birth following IVF, but the rate drops to a little over 10 percent in women over 40.

Fertilization is a numbers game. During ejaculation, hundreds of millions of sperm (spermatozoa) are released into the vagina. Almost immediately, millions of these sperm are overcome by the acidity of the vagina (approximately pH 3.8), and millions more may be blocked from entering the uterus by thick cervical mucus. Of those that do enter, thousands are destroyed by phagocytic uterine leukocytes. Thus, the race into the uterine tubes, which is the most typical site for sperm to encounter the oocyte, is reduced to a few thousand contenders. Their journey—thought to be facilitated by uterine contractions—usually takes from 30 minutes to 2 hours. If the sperm do not encounter an oocyte immediately, they can survive in the uterine tubes for another 3–5 days. Thus, fertilization can still occur if intercourse takes place a few days before ovulation. In comparison, an oocyte can survive independently for only approximately 24 hours following ovulation. Intercourse more than a day after ovulation will therefore usually not result in fertilization.

During the journey, fluids in the female reproductive tract prepare the sperm for fertilization through a process called capacitation, or priming. The fluids improve the motility of the spermatozoa. They also deplete cholesterol molecules embedded in the membrane of the head of the sperm, thinning the membrane in such a way that will help facilitate the release of the lysosomal (digestive) enzymes needed for the sperm to penetrate the oocyte’s exterior once contact is made. Sperm must undergo the process of capacitation in order to have the “capacity” to fertilize an oocyte. If they reach the oocyte before capacitation is complete, they will be unable to penetrate the oocyte’s thick outer layer of cells.