Ovulation is triggered by a surge of luteinizing hormone (LH) that causes a mature follicle in the ovary to rupture and release an egg. In a natural cycle, this surge is set off by rising estrogen levels. In fertility treatment, medications or injections mimic or amplify this hormonal signal to make ovulation happen on a predictable schedule.
How Your Body Triggers Ovulation Naturally
The process starts in the days after your period, when levels of follicle-stimulating hormone (FSH) rise and prompt several small follicles in the ovaries to begin growing. As one follicle becomes dominant, it produces increasing amounts of estrogen. This estrogen does two things: it suppresses the other follicles from competing, and it sends a signal to the brain that a mature egg is almost ready.
For the brain to respond with an LH surge, estrogen must stay above a specific threshold (roughly 200 pg/mL) for about 50 hours. Once that condition is met, the pituitary gland releases a large burst of LH. Ovulation follows about 10 to 12 hours after LH peaks, or roughly 34 to 36 hours after the surge first begins. This is why ovulation predictor kits, which detect the LH surge in urine, can give you a one- to two-day heads-up.
The LH surge doesn’t just crack the follicle open. It also triggers the egg inside to complete its final stage of cell division so it’s ready for fertilization, and it activates enzymes (including collagenase and prostaglandins) that digest the follicle wall, allowing the egg to break free. After release, the egg remains viable for fertilization for about 24 hours.
Oral Medications That Induce Ovulation
When ovulation doesn’t happen on its own, oral medications are typically the first step. The two most common options work by tricking the body into producing more FSH, which pushes follicle growth past the point where the natural LH surge kicks in.
Letrozole temporarily lowers estrogen production, which makes the brain think hormone levels are too low and respond by ramping up FSH. It’s now considered the first-line treatment for people with polycystic ovary syndrome (PCOS). In a major trial published in the New England Journal of Medicine, women with PCOS who took letrozole had a cumulative live birth rate of 27.5%, compared with 19.1% for those who took clomiphene. Letrozole also produced higher ovulation rates overall.
Clomiphene citrate blocks estrogen receptors in the brain, creating a similar effect: the brain senses low estrogen and increases FSH output. Clomiphene has been used for decades and remains effective, but the head-to-head data in PCOS now favors letrozole for both ovulation and live birth rates. For people without PCOS who simply aren’t ovulating regularly, both medications are reasonable starting points.
Injectable Hormones for Harder Cases
When oral medications don’t work, injectable gonadotropins deliver FSH (and sometimes LH) directly into the body, bypassing the brain’s signaling system entirely. These are synthetic or purified versions of the same hormones your pituitary gland normally produces. They directly stimulate follicle growth in the ovaries.
Injectable gonadotropins are the go-to option for people whose brain-ovary hormone axis isn’t functioning at all, since medications like letrozole and clomiphene rely on that axis being intact. They’re also used for people with PCOS or unexplained infertility who didn’t respond to oral treatment. However, they require close monitoring with blood tests and ultrasounds because the ovaries can over-respond.
The risks are meaningfully higher than with oral medications. Multiple pregnancies (twins or more) are 5 to 10 times more likely with injectables, even at low doses. Ovarian hyperstimulation syndrome (OHSS), where the ovaries swell and fluid shifts out of the bloodstream into the abdomen, occurs in a small percentage of oral medication cycles but is far more common with injectables. Mild symptoms include bloating, abdominal pain, and breast tenderness. Severe OHSS is rare but can cause blood clots and requires hospitalization.
The Trigger Shot
Once follicles reach the right size, a “trigger shot” of human chorionic gonadotropin (hCG) is often used to precisely time ovulation. hCG mimics the natural LH surge because the two hormones are structurally similar. In most fertility centers, follicles are considered mature when they measure 17 to 18 mm in diameter on ultrasound, though follicles in the 12 to 19 mm range on the day of the trigger are the most likely to yield a mature egg.
After a trigger shot, ovulation typically occurs between 36 and 40 hours later, with some studies finding the first follicle ruptures at around 38 hours on average. This predictable window is what allows clinicians to schedule intrauterine insemination or egg retrieval with precision. For IVF, the retrieval is usually planned at 34 to 36 hours post-trigger, just before the egg would release on its own.
The Role of Insulin Sensitivity
In people with insulin resistance, particularly those with PCOS, elevated insulin levels can disrupt the hormonal balance needed for ovulation. High insulin drives the ovaries to produce excess androgens (male-type hormones), which interfere with follicle development. Improving insulin sensitivity can restore ovulation in some cases, either on its own or by making ovulation-inducing medications more effective.
Metformin, an insulin-sensitizing medication originally developed for type 2 diabetes, is sometimes used alongside ovulation induction drugs. It appears to improve the uterine lining environment and blood flow to the uterus during the implantation window. Weight loss in insulin-resistant individuals can also lower insulin levels enough to restart ovulation without medication, though this varies widely from person to person.
How Ovulation Is Confirmed
Knowing that ovulation actually happened matters, whether you’re trying to conceive naturally or evaluating whether a medication is working. The most reliable clinical method is a blood test for progesterone. After ovulation, the ruptured follicle transforms into a structure called the corpus luteum, which pumps out progesterone to prepare the uterine lining for a potential pregnancy.
A single blood draw showing progesterone at or above 5 ng/mL confirms ovulation with close to 99% specificity. This test can be taken at a random point in the second half of your cycle, though mid-luteal phase (about a week after expected ovulation) is the traditional timing. At home, a sustained rise in basal body temperature of about 0.5°F after the expected ovulation date reflects this same progesterone increase, though it’s less precise than a blood test.
Ultrasound can also confirm ovulation by showing that a previously tracked dominant follicle has collapsed or disappeared, sometimes with a small amount of fluid visible behind the uterus where the follicle ruptured.