Associate Director, REI
Weill Cornell Medical Center
Yale School of Medicine
Medical Director, REI
The most simple way that reproduction can go wrong is when intercourse isn’t timed so that sperm is where it needs to be before the time of ovulation.
Sperm can live up to five days, but generally speaking, sex should happen in the three days leading up to ovulation to make sure sperm are present in the fallopian tubes at the time of ovulation.
You might be surprised how often people think they’re tracking their cycle to perfect this timing, but still get it wrong—we’ll share more later on about how to optimize this.
Of course, the presence of an egg is non-negotiable in this process. This requires a functioning ovary. There are a few broad buckets where an egg won’t be available.
If ovulation isn’t happening, then mature eggs are not being released into the fallopian tubes, so the rest of the reproductive process can’t happen.
This is often the case when there is a hormonal imbalance, for example, with women who have PCOS. The microscopic follicles in the ovary aren’t getting hormonal signals to grow and develop. Without a dominant follicle growing during a cycle, there won’t be a mature egg released during ovulation.
Women are born with all the eggs they’ll ever have, so if the stockpile of eggs has been completely depleted, the process can’t happen. By the time a woman reaches menopause (at an average age of 51), her ovaries will no longer have any microscopic, egg-containing follicles left. It’s also possible that this could happen before that age because of damage done to the ovaries or primary ovarian insufficiency. It’s pretty rare that a woman of reproductive age would no longer have follicles or eggs in her ovaries.
In this case, even if all the right hormones are released, the ovaries won’t listen. So even if a menopausal woman is given high levels of FSH, it won’t jump-start her ovaries.
Unfortunately, the majority of ovulated eggs are not capable of producing a healthy pregnancy. And the likelihood that a given egg has all the right stuff to produce a healthy baby decreases as a given woman ages—this is the main reason pregnancy rates decrease with a woman’s age and miscarriage rates increase.
To produce a healthy baby, an egg must be of high quality. There are a number of factors that contribute to egg quality, but likely the most important factor is an egg’s ability to mature and develop with the correct number of chromosomes. For the moment just know that being “chromosomally normal” or “euploid” is essential for a healthy pregnancy—this generally becomes less frequent as a woman ages.
Chromosomes carry all of our genes, and it’s hard to overstate how important it is for the viability and health of future children that an egg—and resulting embryo—have the correct number of chromosomes.
Since this is all probably pretty abstract to most of us, it’s easiest to understand through an analogy. Think of DNA as the full book shelf (or, if you remember this far back, an entire encyclopedia set). A chromosome is a single book. Genes are the pages in those books, and mutations are the letters on those pages. If all of us are walking, talking encyclopedia sets, we each have 46 books, or chromosomes, 23 of which are genetically contributed from an egg and 23 contributed from the sperm.
During egg maturation, the crucial process of meiosis takes place—an egg needs to shed half its DNA blueprint, going from 46 to 23 chromosomes, making room to combine with the sperm’s DNA.
In a perfect scenario, division happens evenly. But, as women age, it’s more likely that an uneven division will occur, leaving a mature egg with an extra or missing chromosome. In that case, the resulting embryo will have a number other than 46—this will either result in an embryo that can’t implant, that results in an early miscarriage, or a baby with a chromosomal abnormality like Down syndrome.
If an egg doesn’t have the right number of chromosomes, then it’s not considered high quality enough to lead to a healthy pregnancy.
If the fallopian tubes are blocked or damaged in any way, natural reproduction will be impeded. For example, if a fallopian tube is damaged by scar tissue, it won’t be able to vacuum eggs off of the ovary. Likewise, if the tube is blocked, there will be no place for egg and sperm to meet, so fertilization can’t take place naturally.
Finally, if fertilization has happened in the fallopian tube, the tube needs to then transport that embryo back into the uterus—otherwise, the pregnancy will take place in the tube itself, which is life-threatening and known as an ectopic pregnancy. Tubal function could be compromised for a number of reasons, including smoking, endometriosis, or previous infections like sexually transmitted infections.
Sperm must start in the vagina to eventually end up at the fallopian tubes to meet the egg. This means it must be ejaculated in the right place (the vagina) and at the right time for a pregnancy to be possible.
Sexual dysfunction among men is more common than generally appreciated. Failure to maintain an erection or to achieve ejaculation makes natural pregnancy impossible. And more subtle sexual dysfunction may result in fewer episodes of intercourse which also decreases pregnancy rates.
If there’s not enough sperm, you’ll likely run into problems. You might think that one sperm would be enough to fertilize one egg and, in theory, that’s true. But, in reality, there are lots of obstacles a sperm must overcome to make it to the egg and eventually fertilize it—only one out of every 14 million sperm make it to the fallopian tubes to meet the egg!
Generally there are three reasons someone wouldn’t make enough sperm:
The testicles aren’t being prompted to make sperm
The testisticles are being prompted, but won’t cooperate
The testicles are cooperating, but some blockage keeps the sperm from being ejactulated
If there are literally zero sperm being released, then conception can’t happen without help. If there are some sperm, but less than in the tens of millions, pregnancy is still possible, but it’s less likely to happen on its own.
If sperm aren’t capable of swimming forward, they will never make it where they need to go to find the egg. Likewise, if some sperm survive and make it where they need to go, but they still can’t fertilize the egg. If sperm aren’t capable of both swimming and fertilizing, the natural process can’t proceed.
There are many reasons a uterus might be less likely or unable to support a healthy pregnancy. Some reasons are issues with the anatomy of the uterus itself that makes pregnancy less likely. Others issues have to do with hormonal function or issues with the lining of the uterus that make implantation more difficult.
As far as anatomy, there are several things that could happen to distort the shape or condition of the uterus to make it less likely to support a pregnancy. This includes a uterus of an abnormal shape (like a septate uterus) or distortion due to issues like fibroids, or polyps.
There can also be issues with the uterine lining, called the endometrium, which can be damaged by scar tissue, which can happen from previous D&Cs, C-sections, or any procedures involving the uterus. When there’s scar tissue, the endometrium might not develop sufficiently for implantation and pregnancy to happen. We have a dedicated course on the topic of endometriosis here, but for now, we’ll touch on some high level information.
At times, the endometrium may not receive the hormones it needs to develop or not develop and grow thick even in the presence of the right hormones. Without a thick lining, implantation is harder—there are fewer signals the lining can send to an embryo to bring it in. It becomes less likely that an embryo will “stick” or implant and get the nutrition it needs from endometrial lining that is not thick enough.
Some research suggests that infections of the uterine cavity, sometimes referred to as endometritis, or chronic inflammation, may be associated with implantation issues or miscarriage. Chronic endometritis can be cleared upafter being treated with antibiotics—and for those patients who are able to, they have better results with recurrent miscarriage.
Other new research suggests that the uterine microbiome plays an important role in pregnancy, too. The state of the research there isn’t well developed enough, though, to impact treatments yet.
As you might have gathered, hormones are crucial to the process of reproduction. Like we mentioned earlier, hormones are the conductor of this orchestra, and they set off a cascade of events that follows precise order and timing.
Men need the right concentrations of testosterone, FSH, and LH to produce sperm. Women need to have the right amounts of hormones like FSH, LH, estrogen, and progesterone—and at the right time—to trigger events throughout the cycle from follicle growth to egg maturation, growing the uterine lining, and implantation.
This is where even tiny problems with the amount or timing of hormone release can throw everything off. For example, if progesterone increases just one day too early in the cycle, an embryo may not implant in the uterus. So a potential pregnancy won't happen.