The Bottom Line

Fertilization, or conception, occurs within 12 to 24 hours after ovulation; the blastocyst implants around 6 to 7 days later. Another 24 to 48 hours for HCG to circulate in the blood, and a pregnancy test will become positive.

Knowledge of ovulation is the most valuable piece of information for those trying to become pregnant and engaging in sex at least once within 1 to 3 days before ovulation offers the best chance of pregnancy.

However, even if fertilization occurs, numerous cell divisions and other reactions need to occur for the blastocyst to officially implant and secrete HCG. This process is more likely to fail than succeed in any given cycle, making human reproduction very inefficient. 

In can take several months or longer to become pregnant, which is considered normal.  However, women should consider pre-conception appointments with a health care provider (HCP), who can take lab work to assess for potential problems, answer questions, evaluate nutrition and current medications, conduct an ultrasound prior to pregnancy (fibroids, etc.), and – overall – provide women the best possible head start.

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Background

Each human ovary contains 2 million oocytes (eggs) at birth, and approximately 400,000 at the onset of puberty. These are depleted at a rate of approximately 1,000 follicles per month until age 35, when this rate is believed to accelerate.

Assuming regular ovulation during each month between menstruation onset and menopause, and without contraception use, there are approximately 400 to 480 opportunities for pregnancy in a lifetime.

90% of women have a menstrual cycle between 23 and 35 days. This variation almost solely occurs during the first half of the cycle (proliferative/follicular phase), which can last anywhere from 6 to 20 days.

On average, there is only about a 15% to 20% chance of pregnancy each cycle. Fertilization is a complex sequence of molecular events and any disruption to any stage – even minor – can cause the death of the fertilized egg (even before implantation).

The number of potentially fertile days each month may be as high as 12 days, while the number of days of peak cervical mucus (high probability of pregnancy) appears to be about 6 days. However, there may be substantial variability in number of fertile days between cycles for the same woman.

Effective fertility methods for "timing" include cervical mucus and position and body temperature.

Interestingly, in a study that surveyed more than 400 women seeking information about getting pregnant, these methods were not frequently used (Capotosto and Jurgens; 2020).

The cervical mucus method involves women using either tissue/toilet paper (or their fingers) to assess their cervical mucus. Near ovulation, this mucus becomes clear and stretchy, similar to egg whites (known by the term spinnbarkeit). The cervix will also be higher in the vaginal canal, its firmness will soften, and it will be slightly open to allow for the passage of sperm.

The Basal Body Temperature method includes women checking their body temperature first thing in the morning with a digital thermometer from the beginning of a cycle to the next cycle to identify a pattern. There will be a noticeable increase of approximately 0.5 to 1° F shortly after ovulation. This method can be hard for some women to maintain accurately each day and many different factors can affect body temperature on any given day (Steward and Raja; 2020).

Ovulation

Ovulation is triggered by a surge of luteinizing hormone production; ovulation usually follows within 12 to 24 hours. A woman can still become pregnant if she had sex for up to five days before ovulation, as some sperm may still be alive in the fallopian tubes for this period of time; however, the average is 1 to 3 days.

Usually, only one oocyte is released; if two are released, and fertilized (by different sperm) fraternal twins will result. These children share a womb, but are genetically distinct individuals. Identical twins occurs when one fertilized egg splits into two eggs that are an identical genetic match.

Even though it is estimated that about 6 to 12 oocytes have the potential to be released every month, only one oocyte is released during ovulation most of the time.

The chemical/hormonal process that occurs which results in only one egg being released (as opposed to 6 or more) is not completely understood. However, there are several fertility treatments that promote the release of multiple eggs.

Signs of ovulation (cervical position and mucus, BBT) are generally assessed to be more reliable than its symptom, which has been described as a cramping-type of pain (called mittelschmerz, or "middle pain") on the side of the abdomen where ovulation occurs; it can occur before, during, or just after ovulation. It is estimated that up to 40% of women of reproductive age experience this symptom.

Mittelschmerz can occur every month, or just every few cycles, and usually goes away within three to twelve hours. Some women can experience such severe or intense pain that it may be mistaken for appendicitis.

The exact reason for the pain is not known, but tubal or uterine spasm, or increased tension in the ovary is one theory. Another theory includes irritation within the abdomen from the discharge of blood and fluid from the ruptured follicle.

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Fertilization

On average, as many as 300 to 350 million sperm (3.5 milliliters of semen) may be ejaculated into the vagina during sex, but only a few hundred make it to the Fallopian tube.

An animal study published in May 2021 found that motile cilia (hair-like projections) and smooth muscle participate in transporting the fertilized egg and sperm through the Fallopian tube. Motile cilia are required for egg pickup, whereas smooth muscle contraction is more important for sperm and embryo transport. (Knowing this mechanism of early embryo transport within the Fallopian tube is critical because disrupted transport is known to lead to female infertility and ectopic pregnancy.)

The oocyte is usually fertilized 12 hours after ovulation and can occur in different parts of the Fallopian tube, but not the uterus (fertilization must occur well before arrival in the uterus).

Fertilization.
Blausen.com staff (2014). DOI:10.15347/wjm/2014.010. ISSN 2002-4436.

After ovulation, the follicle that released the egg develops into the corpus luteum (CL). The CL produces hormones for establishing and maintaining a pregnancy. If implantation does not occur, the CL will degenerate (die), and menstruation will begin.

The most important step in fertilization is the passage of the sperm through the oocyte wall (zona pellucida). Immediate changes then occur in the wall’s properties that stop other sperm from entering. Complete fertilization takes about 24 hours. The resulting zygote has half its chromosomes from the mother, and half from the father.

The sex of the baby is determined at fertilization. Males have X and Y sperm, and each are formed in equal numbers. All oocytes are X. If an X sperm fertilizes the oocyte, the child has female reproductive organs (XX); if a Y sperm fertilizes the oocyte, the fetus will have male reproductive organs (XY).

The widely held belief that X sperm are generally slower than Y sperm has never been confirmed. The belief started in the 1960s – and seemed true in various experiments – until computer assisted sperm analysis indicated there are no differences between the two.

Implantation

Scientists still do not completely understand all the chemical and molecular events that lead to successful implantation.

Current knowledge indicates that after ovulation and fertilization, the embryo remains in the middle portion of the Fallopian tube while it undergoes a sequence of cell divisions. Cell division occurs through mitosis, where two cells divide into another two cells, and so on. These cell divisions are not dependent on hormones, which is why they can also occur in a lab (in vitro).

About 30 hours after fertilization, the zygote continues to divide into additional cells called blastomeres, becoming a compact ball. The zygote travels toward the uterus, through the final portion of the Fallopian tube, for approximately 10 hours. By this time, the zygote is now a morula (about 16 cells) which is Latin for mulberry, based on its appearance.

Even though the morula continues to divide and obtains more individual cells, the cells just get smaller as they divide, and therefore the morula does not actually get any bigger. A fluid filled cavity then opens in the morula, and it becomes a blastocyst.

Morula (left) vs. Human blastocyst (right, with cavity)

During the menstrual cycle, the uterine lining is only receptive to implantation for a short window of time. The most optimal time is known as the window of implantation which is cycle days 20 through 24 (with a 28-day cycle) or 6 to 10 days after ovulation.

Studies have been conducted to determine the most optimal endometrial thickness for implantation, to include the minimum thickness required to support a pregnancy, but no consensus has been reached.

Did you know: Many similarities exist between blastocyst implantation and cancer cells. 

Trophoblast cells (cells that develop the placenta) behave in a temporary invasive manner in order to invade the uterine lining. This process is similar to cancer cells, except it is temporary and the invasion ends at the endometrial layer of the uterus. (Dhar et al., 2021; pre-print).

However, in some cases (very rarely), this invasion can lead to a cancer collectively known as Gestational Trophoblastic Disease.

The total time from ovulation to the blastocyst entering the uterus is about 4 days. The blastocyst finds a location at which to implant which is guided by chemical properties of the endometrium. The entire surface of the blastocyst has the potential to attach as it floats around freely. Once the blastocyst attaches, it cannot be dislodged (miscarriage is a different mechanism).

The blastocyst is completely embedded within the endometrium within 6 to 10 days after ovulation (matching the WOI).
Scientific Animation. CC BY-SA 4.0

After implantation, the blastocyst separates into two parts: the trophoblast (creates the placenta) and the embryoblast (creates the embryo).

The embryo actively secretes human chorionic gonadtropin (HCG) after implantation, which is detected in home pregnancy tests. This HCG secretion also “rescues” the CL which will continue to secrete progesterone until the placenta completely takes over around 8 to 12 weeks of pregnancy.

At implantation, the embryo is approximately 0.01 to 0.2 millimeters in length.

Signs and symptoms of implantation:

Implantation can lead to cramping and/or light vaginal bleeding usually described as brownish in color (due to it being “older” blood) and is likely to occur closer to a woman’s expected period.

There is very little research on implantation bleeding, and although it can happen, it does not appear to be very common (Promes et al., 2010; Harville et al., 2003; Feier, 2008).

Action

It is recommended that women call their HCP as soon as they get a positive home pregnancy test or if they believe they may be pregnant. Although most first appointments will not be for another few weeks, for some women, an HCP may want to see them earlier for possible information/counseling, blood work, pregnancy confirmation, or an immediate change in medication regimen.

Women who are not yet pregnant should consider a pre-conception appointment with their HCP, who can take lab work (i.e. thyroid), answer questions, evaluate nutrition and current medications, conduct an ultrasound prior to pregnancy (possible uterine concerns) and – overall –provide women the best possible head start.

At the first prenatal appointment, HCPs will confirm their due date based the first day of their last menstrual period and/or after ultrasound assessment. Women should read more about Due Date and Gestation to learn what this means and when they can actually expect the baby to arrive.

For women who have just learned they are pregnant, it is estimated that up to 90% of women will experience nausea and vomiting of pregnancy ("morning sickness"), beginning as early as 4 to 6 weeks. The most optimal way to manage these symptoms is to learn about the condition early, apply management techniques early, and get an HCP involved early. Read more to learn why.

Women should consider sharing their experience below of when/how they found out they were pregnant, whether they had any early signs or clues, and how they felt. The experiences page is meant to be a positive place for support and provides women different perspectives of pregnancy they may find valuable.

Resources

Short time-lapse video of in-vitro fertilization and initial cell division:

References

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