One of the most fascinating aspects of human reproductive physiology is the inefficiency of the female menstrual cycle, and understanding the menstrual cycle and its complexities is the first step to understanding female fertility. Dr. Nicole Marchetto, Reproductive Endocrinologist and Infertility Specialist at Shady Grove Fertility in Pennsylvania and Delaware, breaks it down to give us an in depth understanding of what happens each month.
The purpose of the menstrual cycle is to give the body an opportunity to focus its energy into growing one egg for the month for a chance to get pregnant. It involves a series of hormonal changes occurring both in the ovary and the uterus with that goal in mind.
Individuals born with a uterus and ovaries typically start their menstrual cycles around puberty and continue until menopause.
Ovarian Reserve
Part of understanding the menstrual cycle and fertility is understanding the concept of ovarian reserve.
Women are endowed with a finite number of eggs. When a female fetus is developing in her mother’s womb, she starts with a very large pool of eggs, 5-7 million eggs. This vast but finite number of eggs forms the initial ovarian reserve for that individual, but that pool is depleted irreversibly as she ages. By the time a woman is born, that number has declined to about 1-2 million and once she reaches puberty, it has decreased to about 100,000-400,000, and continues to fall until the menopausal transition, which is marked by the exhaustion of that pool, when there may be only around 1,000 remaining.
Ovarian reserve is a concept that involves both egg quantity and egg quality. Both decline as women age. Quantity involves that finite number a woman was born with, and the attrition throughout her lifespan. Quality refers to the health, genetic integrity and developmental potential of a woman’s eggs and involves the ability of that egg to lead to a successful pregnancy.
There are two main changes happening throughout a woman’s lifecycle with respect to ovarian reserve:
- We are losing a dramatic number of eggs throughout our lifetime. We are losing them in a very wasteful way. Each month it’s as if your body understands that the eggs are a commodity, and it has rationed out an allotment for that cycle. That is all that’s available for that month. The goal of the menstrual cycle is to try to get one of those eggs to grow and the body focuses its energy into growing that one egg. The rest of the eggs in that month’s batch, however, die off. We don’t use them. It’s exceedingly wasteful, as we will not be able to generate any more of these eggs in our lifetime.
- Egg quality declines as we age. Eggs, like other cells in the body, age with time and become increasingly abnormal as we get older. We estimate that any given time in our reproductive lifespan, there is a percentage of abnormal eggs in that month’s batch.
By age 35, roughly 30% of the eggs in the batch are abnormal. By 38, about 50%. By 40 years old, about 70-75% of the eggs are abnormal and by 42, 90-95%. An abnormal egg is one that will not likely result in a successful pregnancy. An abnormal egg may still grow and be ovulated in a month, but if it does meet up with a sperm, that embryo is more likely to lead to something like a miscarriage, a pregnancy complicated by an abnormal number of chromosomes, or a pregnancy that just does not successfully implant.
We know that not only do we waste a tremendous number of eggs in our lifetime, but we also do not have a specific mechanism by which we can choose the best egg in the batch for any given month. Rather, the selection process is somewhat arbitrary, meaning that as we get older, the chance of an abnormal egg is statistically higher based on the proportion of abnormal eggs in the batch at any given time.
This means that as we age, the chance of infertility goes up, chance of miscarriage, pregnancy complications, and chromosomal aberrations all increase, statistically, and this is really a factor of egg quality.
Together, these factors contribute to the incredible inefficiency of human’s reproduction. In our peak reproductive years, in someone who does not have a diagnosis of infertility, the chance of achieving a pregnancy within one menstrual cycle is at best about 20%.
The Menstrual Cycle
The menstrual cycle is roughly the length of a one month. On average, a normal cycle ranges from 21-34 days. Cycle day 1 is marked by the first day of full flow. The last day of the cycle is the day before you start bleeding again with the next period.
At the beginning of the cycle, the brain instigates changes aimed at nurturing one egg for potential fertilization. It does so by signaling to the ovaries through Follicle Stimulating Hormone (FSH), essentially requesting egg production. Within the ovaries, each egg resides within a fluid-filled sac known as a follicle, so FSH is appropriately named. In response to FSH, the ovaries select one follicle from the batch, regardless of its quality, to nurture to maturity.
Over the initial 7-10 days of the ovarian menstrual cycle, the chosen follicle grows, reaching a diameter of approximately 2cm. While this growth is observable via ultrasound, the brain remains unaware. Thus, the follicle signals its progress by releasing increasing amounts of estrogen. Estrogen not only communicates with the brain but also grows the uterine lining, the endometrium, to provide space to support a potential pregnancy, akin to tilling soil in a garden before planting.
Sensing the elevated estrogen levels, the brain signals with a surge of Luteinizing Hormone (LH) to cause the egg to complete the last step of maturation and to call the ovary to release the egg in the event known of as ovulation. That hormonal surge is the target for over-the-counter ovulation predictor kits, which detect high levels of LH in the urine. The free egg is then picked up by the fallopian tube, primed for fertilization, where it waits for a potential sperm.
Simultaneously, the now-empty follicle transforms into the Corpus Luteum, a temporary structure that secretes Progesterone. This hormone further readies the uterine lining for potential pregnancy, sustaining it until the placenta assumes this role.
If sperm is introduced into the picture either by intercourse around ovulation, or by artificial insemination, then the sperm may be available to make the journey through a jungle of cervical mucus, all the way through the cavity, to meet up with the egg in the fallopian tube. It is a difficult journey and many of the sperm die off in the process. If one makes it, then it can potentially fertilize that egg.
If the egg is successfully fertilized, now that fertilized egg has to begin its journey to becoming an embryo and travel back into the cavity. That journey takes about 5 days and all the while, it’s dividing. It begins as 1 cell, half sperm, half egg. By the time it gets into the cavity, it’s a bundle of about 200 cells, called a blastocyst, which is the stage at which it is capable of implanting.
If the embryo implants, that marks the beginning of the pregnancy, and the pregnancy hormone HCG will begin to be generated as a message to the brain to not shed the uterine lining. That message will also be delivered to the corpus luteum and will ask it to continue making more progesterone until the placenta is big enough to make its own, which takes about 7-9 weeks.
If there is no pregnancy, perhaps the tube was blocked and the sperm didn’t make it to the egg, or the egg was an abnormal egg that month, then there is no HCG hormone and the brain gets the message that it didn’t work this month, and tells the factory, we don’t need you anymore. The factory disassembles its team, and the progesterone falls, and it is the fall in progesterone that signals the uterus to shed that lining. The lining being shed marks cycle day 1 of the next cycle which brings a new batch of eggs to try it all again.