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When puberty begins, males produce sperm in their testes with the help of the hormone testosterone. The sperm then travel through the epididymis, vas deferens, ejaculatory duct, and urethra before exiting through the tip of the penis during an ejaculation. An ejaculate includes the sperm and an alkaline (non-acidic) fluid called semen.
Women are born with all of the eggs that they will ever have. When puberty begins, menstrual cycles occur to prepare the body for pregnancy every 28ish days. Typically, 1 mature egg is released from its follicle in the ovary during ovulation and moves into the Fallopian tube (where fertilization can occur), and then to the uterus (where implantation can occur). If implantation does not occur, the uterus sheds its endometrial lining, and a period occurs.
A brief note: sperm and eggs are known as haploid cells, meaning that they only have 1 set of DNA (all other cells have 2 sets). When a sperm fertilizes an egg, the two individual sets of DNA combine to make an embryo with 2 set of DNA (diploid).
For natural fertilization to occur, the sperm must be ejaculated into the female reproductive tract while a mature egg is in the Fallopian tube (right after ovulation). Ejaculated sperm travel through the female's vagina, cervix, and uterus before reaching the egg in the Fallopian tube. The sperm go through a process known as capacitation as they travel to the egg, which makes them able to achieve fertilization.
A normal ejaculate contains millions of sperm, but only one sperm fertilizes the egg. To achieve fertilization, this sperm travels through granulosa cells (residual cells from the follicle that surround the egg), penetrates the egg's outer shell (zona pellucida), and fuses with the egg's plasma membrane. This process blocks any other sperm from entering the egg. The sperm then deposits its DNA into the egg (which is now called a zygote) so it has 2 sets of DNA (diploid).
The zygote (which quickly becomes known as an embryo) spends the next few days traveling down the Fallopian tube and eventually makes its way into the uterus. Along the way, the embryo divides from 1 cell to 2, then 4, etc. until it is made up of over 150 cells! At that point, the embryo hatches out of its outer shell (zona pellucida) so that it can implant in the endometrial lining.
The thick and vascular endometrial lining is the perfect environment for embryo implantation. The embryo burrows into the endometrial lining and begins to secrete the hormone hCG (human chorionic gonadotropin), while the corpus luteum (from the follicle in the ovary) continues to secrete progesterone and estrogen to keep the pregnancy going. The embryo will eventually form its placenta, which will take over progesterone secretion from the corpus luteum.
Well, now we know all about reproduction! But what happens when things go wrong? Let's take a look at some causes of infertility once the sperm enters the female reproductive tract.
Vaginal issues: the sperm first travel through the vagina on their way to the egg. The vagina is naturally an acidic environment (to protect it from harmful bacteria and viruses like HPV), but it becomes less acidic during sex. Furthermore, semen is an alkaline (non-acidic) fluid. The decreased vaginal acidity mixed with the alkaline semen make the vagina a suitable environment for sperm passage during sex. Sometimes, though, issues arise that increase the vagina's pH so harmful bacteria/viruses can survive in it. For example, bacterial vaginosis is an overgrowth of harmful bacteria in the vagina that can damage the vagina and/or sperm. Antibiotics can help ward off the harmful bacteria, but these can also kill the good bacteria in the vagina, so vaginal probiotics may be needed, as well.
Cervical issues: the sperm's next stop on its way to the egg is the cervix. The cervix is lined with cells that secrete mucus. Around the time of ovulation, the mucus is thin so the sperm can easily swim through it. Otherwise, the mucus is thick to prevent sperm from entering the uterus. But sometimes the mucus is either too thick or too scant, which interferes with sperm transport. This is typically caused by hormonal imbalances or cervical scarring. The mucus can also sometimes contain antibodies that attack the sperm as it tries to swim through the cervix. Additionally, the cervix can be too thin or completely closed off in a condition known as cervical stenosis. In most of these issues, intrauterine inseminations (IUIs) or IVF can be used to bypass cervical issues.
Uterine issues: the sperm's next stop is the uterus. Typically, the sperm use their tails to swim through the uterus to the Fallopian tube. Sometimes, though, growths such as fibroids or polyps can interfere with the sperm's movement through the uterus. These can be removed with corrective surgery, or an IUI can help facilitate sperm movement into the Fallopian tubes to bypass uterine issues.
Fallopian tube issues: the sperm finally reach the egg in the Fallopian tube, where fertilization naturally occurs. But sometimes there are obstructions that prevent the sperm from reaching the egg. For example, pelvic inflammatory disease or endometriosis can cause scarring or fluid buildup (hydrosalpinx) in the Fallopian tube(s). If only one tube is blocked, natural conception may still be possible. Corrective surgery may be able to unblock the tube(s), or IVF can completely bypass the obstruction(s) to achieve pregnancy. A tubal ligation (tied tubes) closes the Fallopian tube(s) to prevent pregnancy from occurring. Sometimes an embryo can implant in the Fallopian tubes (ectopic pregnancy), but these pregnancies are life-threatening and unfortunately must be terminated.
Implantation issues: once the embryo reaches the uterus, it should implant into the thick, vascular endometrial lining. In some cases, though, the lining is not suitable for embryo implantation. This is typically caused by a hormonal imbalance and can be treated with hormone replacement therapy. The embryo may also not be able implant due to endometrial polyps/fibroids and/or scarring. These can be removed surgically, but a gestational carrier (surrogate) may be needed to carry a pregnancy for women with extreme uterine issues.
Fertilization - Molecular Biology of the Cell - NCBI Bookshelf (nih.gov)
Fertilization - Embryology (unsw.edu.au)
Bacterial Vaginosis and Fertility | American Pregnancy Association
How Does Sex Change Your Vagina’s pH? (forbes.com)
Cervical Factor Infertility – Reproductive Care Center (fertilitydr.com)
Uterine Infertility - Causes, Symptoms, Diagnosis and Treatment (medic-journal.com)
