Fertility Literacy: A Few Key Terms

Usually shortened to REI, Reproductive Endocrinology and Infertility is the medical subspecialty focused on reproductive disorders and the diagnosis and treatment of infertility.

A Reproductive Endocrinologist (RE) is a physician who specializes in reproductive medicine and infertility. REI is a subspecialty of Obstetrics and Gynecology (OB-GYN). 

In the United States, an RE completes medical school, a four-year OB-GYN residency, and then a three-year fellowship in Reproductive Endocrinology and Infertility.

Following this extensive training, physicians pursuing board certification complete rigorous examinations designed to demonstrate their knowledge and clinical expertise in the field.

In short, REs undergo years of highly specialized education and training before caring for fertility patients.

ART stands for Assisted Reproductive Technology and refers to medical procedures used to help achieve a pregnancy. IVF is one example of ART.

LMP stands for Last Menstrual Period. In REI, we live and die by periods!

“Day 1” of the menstrual cycle is generally the first day of full-flow bleeding — spotting does not count. An easy rule of thumb is the first day you need a tampon, pad, or menstrual cup.

Cycle Day is counted from that first day of full flow.

For example, a woman starts spotting over the weekend but does not have full-flow bleeding until Monday morning. Monday is her LMP and Cycle Day 1.

If today is Thursday of the same week, she is Cycle Day 4, sometimes written as CD4 or D4.

Important: Cycle Day tells you how many days have passed since the period began — not how many days the patient has been actively bleeding.

Once Day 1 has been established, the number of days she actually bleeds does not determine her cycle length. Cycle length is counted from the first day of one period to the first day of the next. For example, if periods begin 28 days apart, that is a 28-day menstrual cycle.

If your doctor asks about the duration of your period, that refers to how many days you typically bleed.

One practical note: clinics may have their own rules about what counts as Cycle Day 1 — particularly when full-flow bleeding begins late in the day — so always follow your clinic’s instructions.

More than you ever wanted to know about periods, right? Buckle up! We're just getting started. 

The term "cycle" can be confusing because its meaning depends on the context.

It may refer to your menstrual cycle. For example:
“My cycle is 28 days long.” Or “I’m on Day 4 of my cycle.”

Or it may refer to a treatment cycle, such as an IUI cycle, IVF cycle, donor egg cycle, or other fertility treatment. For example: “I’ve had three IVF cycles.”

In REI, you’ll hear the word cycle used both ways, so context matters.

Follicles are structures in the ovary that contain eggs. Once a follicle reaches the antral stage, it develops a fluid-filled space and begins to look a bit like one of the individual compartments in bubble wrap.

A woman is born with essentially all the eggs she will ever have. At birth, there are roughly 1 to 2 million. By puberty, approximately 300,000 to 500,000 remain.

Most will never ovulate. Instead, they are gradually lost through a natural process called atresia. They break down and are absorbed by the body.

This is important: we are not using up one egg every month. Only one follicle usually makes it all the way to ovulation, but many others are developing and being lost to atresia along the way. Over a lifetime, only a tiny fraction of all the eggs a woman is born with will ever ovulate.

And here is another thing that surprises people: menopause does not mean the ovaries are literally empty. There may still be eggs left, but by that point very few follicles remain capable of responding normally, and the eggs that remain are much more likely to have age-related abnormalities.

So ovarian aging is really about both quantity and quality. We lose eggs throughout life, and the eggs that remain age right along with us.

Note: This is very different from sperm. Sperm production does not begin until adolescence and generally continues for the remainder of his life, although sperm quantity and quality can decline with age.

The earliest, dormant follicles are called primordial follicles. Each contains an immature egg, or oocyte. Over time, groups of follicles begin a long process of growth and development. Eventually, some reach the antral follicle stage, when they can be seen and measured by ultrasound. Follicles appear as dark circles within the grayish image of the ovary.

During a typical menstrual cycle, a group, or cohort, of antral follicles is recruited to continue growing under the influence of hormones, particularly follicle-stimulating hormone (FSH). Usually, one becomes the dominant follicle and continues toward ovulation, while the others stop developing and undergo atresia.

During the follicular phase, the developing dominant follicle produces estrogen, which stimulates the lining of the uterus, called the endometrium. Estrogen causes the endometrium to grow and thicken.

As estrogen rises and remains high enough, it triggers a surge of luteinizing hormone (LH). The LH surge causes important final changes in the egg, helps separate it from the follicle wall, and initiates the process that causes the follicle to rupture and release the egg.

That release of the egg is ovulation.

After ovulation, the egg is picked up by the fallopian tube. It remains capable of being fertilized for roughly 24 hours. If sperm are present, fertilization usually occurs in the fallopian tube.

Meanwhile, the follicle that released the egg transforms into the corpus luteum.

The corpus luteum produces progesterone, which changes the endometrium from a lining that is simply growing into one that is prepared to support implantation and an early pregnancy.

At fertilization, the egg contributes 23 chromosomes, including an X chromosome. The sperm contributes another 23 chromosomes and carries either an X or a Y chromosome. (That means the sperm determines the embryo’s chromosomal sex, typically 46,XX or 46,XY.)

Once fertilization occurs, the single-celled embryo is called a zygote.

The zygote begins dividing almost immediately as it travels through the fallopian tube toward the uterus. It does not tumble down the tube like a stone falling down a rocky hill. Mother Nature doesn't trust gravity to do the job. Rather; it is carried along by the coordinated movement of tiny hair-like cilia lining the fallopian tube, gentle muscular contractions of the tube, and the surrounding tubal fluid. You can think of it as being gently carried or “floated” toward the uterus while it continues to develop.

During this “lazy river” journey, the embryo keeps dividing. It progresses from a single-cell zygote to a cluster of dividing cells, and then to a compact ball of cells called a morula.

As development continues, fluid begins to collect inside the embryo and it becomes a blastocyst. By this stage, the cells have organized into two distinct groups. The inner cell mass (ICM) will give rise to the developing embryo and eventually the fetus. The trophectoderm (TE) is the outer layer of cells that will contribute to the placenta and supporting membranes.

The embryo enters the uterine cavity while still developing and reaches the blastocyst stage before attaching to and implanting in the endometrium.

Once implantation begins, cells associated with the developing pregnancy begin producing human chorionic gonadotropin (hCG), which is the hormone detected by pregnancy tests.

hCG signals the corpus luteum to continue producing progesterone, which helps maintain the endometrium and support the early pregnancy. Eventually, the placenta takes over progesterone production.

If pregnancy does not occur, the corpus luteum degenerates. Progesterone and estrogen levels fall, and that hormonal withdrawal causes the endometrium to shed.

That shedding is the beginning of the next menstrual period... and the cycle starts all over.

 An IUI is a procedure in which prepared sperm is placed directly into the uterine cavity, bypassing the vagina and cervix. In years past, this was commonly called “artificial insemination.”

Donor sperm may be used for an IUI when there is no male partner, or when a male partner does not produce an adequate number of usable sperm.

With an IUI, fertilization still takes place inside the woman’s body. This is called in vivo, which literally means “within the living.”

Keep that term in mind, because it is the opposite of in vitro, which means “in glass” and refers to something taking place outside the body, as it does with IVF.

In Vitro Fertilization (IVF)

IVF is a procedure in which a woman’s eggs are retrieved from her ovaries and fertilized in an embryology laboratory rather than inside the body.

Remember in vivo, meaning “within the living”? In vitro literally means “in glass.” In other words, fertilization takes place outside the body.

An IVF cycle differs from a natural menstrual cycle in two crucial ways:

First, we want more than one egg. Preferably lots more. 

In a natural menstrual cycle, a cohort of antral follicles begins developing, but usually only one breaks away from the pack, becomes the dominant follicle, and goes on to ovulate a single egg. The others undergo atresia and are lost.

In an IVF cycle, we are trying to rescue more of that month’s available cohort. Rather than allowing one follicle to become dominant while the others fade away, injectable medications encourage multiple follicles to continue growing toward maturity together.

We are not creating new eggs (there is no medicine that can do that). Also it's important to understand IVF is not "wasteful" in that we are not pulling eggs out of storage that would otherwise have been available in future months. We are trying to mature more of the follicles that were already in play that month that would otherwise never get used. 

Second, there is no ovulating in IVF.

Just like there is “no crying in baseball,” there is no ovulating in IVF. If the eggs ovulate, they leave the follicles and we cannot retrieve them. Egg retrieval has to happen before ovulation.

So, IVF becomes a driving a car with foot on both gas and brakes situation.

The gas is the stimulation medication. It pushes multiple follicles to grow and mature at the same time. The brakes are medications used to prevent the body from releasing those eggs before we are ready.

And because we are pushing multiple follicles toward maturity while simultaneously preventing ovulation, the cycle requires careful monitoring with ultrasound and hormone levels and start, stop, adjust or change medications, based on that day's test results. 

When the follicles are ready, a trigger medication causes the eggs to complete the final steps of maturation and starts the biological countdown toward ovulation.

The egg retrieval is carefully timed to occur before that ovulation happens.

During the egg retrieval, or transvaginal oocyte retrieval (TVOR), the patient is typically sedated while the physician uses a transvaginal ultrasound to guide a needle into each accessible follicle. The follicular fluid is aspirated and passed to the embryology laboratory, where the embryologist searches for the eggs.

Once the eggs are retrieved, fertilization takes place in the embryology laboratory.

With conventional insemination, prepared sperm and eggs are placed together in a culture dish. The sperm essentially “duke it out” in the dish, much as they would inside the reproductive tract, and one sperm must successfully penetrate and fertilize the egg.

Another method is ICSI, or intracytoplasmic sperm injection, in which an embryologist selects a single sperm and injects it directly into the egg. More on that below. 

Intracytoplasmic Sperm Injection (see the image at top of this page)

ICSI, pronounced “ick-see,” is an additional laboratory step that may be used during an IVF cycle to assist fertilization.

Rather than simply placing eggs and sperm together in the same dish, ICSI involves manipulation. The embryologist physically injects a single sperm directly into each mature egg.

This allows the sperm to bypass the egg’s outer shell, called the zona pellucida, but it does not guarantee that the egg will fertilize.

ICSI takes place entirely in the embryology lab. From the patient’s perspective, there is no difference in the retrieval procedure or recovery, other than the fact that ICSI is usually an additional charge.