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Can IVF decrease the probability of trisomy in the fetuses of older mothers?

Can IVF decrease the probability of trisomy in the fetuses of older mothers?


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Is trisomy mostly due to complications with fertilization?

If so, does in vitro fertilization reduce the probability of trisomy for the fetuses of older mothers?

If not, can zygotes be screened before in vitro fertilization?


Trisomy is due to non-disjunction in meiosis (the process in which eggs and sperm are created). This happens before fertilization.

Trisomies are more frequently seen in children of older women. It's not fully understood why this happens, but it is likely related to the fact that the oocytes do not complete meiosis (and become eggs) until ovulation. Here's an interesting paper that examines the physical causes of non-disjunction, but you might want to read up a bit more on meiosis (depending on your background) before tackling it.

You might screen for nondisjunction, but I don't think it's possible without killing the cells. See the Wikipedia page on karyotyping, which explains how an amniocentesis might be used for a prenatal genetic diagnosis. I don't know the regenerative capabilities of the human blastocyst, but if you had enough cells for a test, I don't think the blastocyst would develop normally.


Down syndrome

Down syndrome (or Down's syndrome) was named after John Langdon Down (1828-1896), who was the first physician to identify it, in 1866.

Down syndrome occurs in about 1 out of every 700-900 live births worldwide (depending on contraception and termination attitudes in different communities), to mothers of all social, economic and racial groups, and is the most common genetic cause of developmental disability.

In the UK around one in every 1000 babies will be born with Down syndrome and there are 60,000 people in the UK living with the condition.

Although the chance of a baby having Down syndrome is higher for older mothers, more babies with Down syndrome are born to younger women. This is because women under 35 make up the majority of the child-bearing population.


Preimplantation genetic screening reduces successful pregnancies after IVF

Preimplantation genetic screening of embryos for chromosome abnormalities reduces the success rate of in vitro fertilisation (IVF) by nearly a third in older women, according to a European study (New England Journal of Medicine 2007356:9-17).

The study looked at the rates of ongoing pregnancies and live births in a total of 408 women aged 35 to 41 years undergoing a total of 862 cycles of in vitro fertilisation. Half of the women (206) were randomised to undergo preimplantation genetic screening, and the other half were a control group and were not screened. Screening involved taking a biopsy of one cell at three days and testing chromosomes to detect trisomies or other abnormalities in chromosome number.

Sebastiaan Mastenbroek, from the Center for Reproductive Medicine at the University of Amsterdam, the Netherlands, and lead author of the study, explained the rationale, “Pregnancy rates in women of advanced maternal age undergoing IVF are disappointingly low. A potential cause is the increased incidence of chromosomal abnormalities. It has been suggested that use of preimplantation screening of cleavage stage embryos for aneuploidies may improve the effectiveness of IVF in these women.”

The results showed a significantly lower rate of pregnancies in the women who underwent genetic screening, however. Only 25% achieved ongoing pregnancies, compared with 37% of women who were not screened (rate ratio 0.69, 95% confidence interval 0.51 to 0.93).

The women randomised to preimplantation genetic screening also had a significantly lower rate of live births, at 24%, compared with 35% in women who were not screened (0.68, 0.50 to 0.92).

Dr Mastenbroek reported, “The study showed that preimplantation genetic screening did not increase, but instead significantly reduced, the ongoing pregnancy and live births after IVF in women of advanced maternal age.”

He concluded, “These results argue strongly against routinely performing preimplantation genetic screening as an adjunct to IVF in this group of women.” Because the study looked at screening in only older women, however, he said that they may not apply to younger women with other indications for preimplantation genetic screening.

“The results suggest that for every nine women who are 35 to 41 years of age who plan three cycles of IVF or IVF and intracytoplasmic sperm injection, there will be one more live birth if preimplantation genetic diagnosis for aneuploidy screening is not performed,” said John Collins, from the Faculty of Health Sciences, McMaster University, Hamilton, Canada, in an editorial in the same issue (p 61).

These results should be broadly generalisable to women of similar age, he considered. “Given the findings, preimplantation genetic diagnosis should not be performed solely because of advanced maternal age.”

Preimplantation genetic diagnosis may reduce the potential for a successful pregnancy for several reasons, Dr Mastenbroek said. The biopsy of a blastomere may reduce the potential of an embryo to successfully implant into the uterus wall. Limitations in the numbers of chromosomes that can be analysed with the technique used in the study may mean that embryos labelled as normal were, in reality, aneuploid for one or more chromosomes not tested.

Finally, human embryos resulting from in vitro fertilisation may be mosaic, so that the chromosomal make-up shown by analysing the blastomere may not reflect that of the entire embryo.

Peter Braude, head of the department of women's health, at King's College, London, and director of the centre for preimplantation genetic diagnosis, at Guy's and St Thomas' Foundation Trust, London, thought it was important to distinguish between prenatal genetic screening (PGS) and prenatal genetic diagnosis (PGD).

“Prenatal genetic diagnosis was developed to help couples who had recurrent known genetic disease that would put their offspring at risk of being affected by the disorder,” he explained. These patients are usually fertile and are choosing prenatal genetic diagnosis as a way of avoiding having to confront termination of pregnancy or an affected child.

“This is in sharp contrast with screening for sporadic risk of aneuploidy in order to try to improve success of IVF in older, infertile patients,” Professor Braude said. “These patients have no prior genetic risk but are trying to screen out any embryos that have a sufficient aneuploidy to result in failure of implantation, miscarriage, or a survivable single aneuploidy more commonly seen in older women, such as Down's syndrome [trisomy 21]. Hence the use of the term ‘preimplantation genetic screening.'”

Prenatal genetic screening has been widely used, especially in the United States, in the belief that it must improve the odds in women who have a reduced chance of conception because of age.

Sjoerd Repping, associate professor in reproductive biology and director of the in vitro fertilisation laboratory of the Center for Reproductive Medicine, Academic Medical Center, Amsterdam, and one of the researchers, said, “PGS is an expensive technique that is very frequently offered to women of advanced maternal age under the statement that it will increase pregnancy rates. The fact that the data shows that it does not—on the contrary, it decreases pregnancy rates—should be included in the counselling of these patients undergoing IVF treatment.”

Professor Braude agreed, “The key here is that the evidence just does not support continued use of prenatal genetic screening for advanced maternal age.”

He added, �spite the fact that we are the largest and most successful PGD unit in the country, having done over 400 collections with over 100 babies born healthy after testing for a variety of genetic conditions, we have never undertaken PGS as we have always had grave doubts over its efficacy.”


The Role of Age in Fertility

Age plays an important role in fertility. Your chances of being able to get pregnant naturally start to lower slightly in your late 20s, and considerably in your late 30s. Once you hit 40, your chances of conceiving can drop to 5-10%. By the age of 45, the chance of pregnancy drops to less than 5%.

These are statistics for the general population, but there’s always room for outliers. There are instances where a 24-year-old can be struggling to conceive, while older women approaching menopause can have an unexpected pregnancy.

Risks

It’s essential to understand how your age impacts your fertility when you are trying to conceive (TTC) or thinking about conceiving soon. Here are some of the ways in which your age may impact the risks of pregnancy.

Miscarriage

The risk of having a miscarriage in your 40s is nearly 50%, more than three times that of a woman in her 20s. The younger you are, the less likely you are to miscarry, given that you are otherwise healthy. That’s because the genetic mutations that cause most miscarriages become more common as women age. It’s estimated that half of all miscarriages are caused by extra or missing chromosomes.

Pregnancy Complications

Certain complications in the mom or the baby become more common as women age. For example:

    is a syndrome combining high blood pressure with signs of kidney and liver damage during pregnancy. It is more common in mothers aged 40 and older.
  • Premature birth (birth before 37 weeks gestation) frequently causes low birth weight, which can lead to complications in the health of the infant. Research suggests that women over age 40 are more likely to give birth prematurely.
  • Some women develop high blood sugar during pregnancy, known as gestational diabetes, which increases their risk of developing type II diabetes later in life. Compared with women ages 20 to 29, women in their 40s are three to six times more likely to develop gestational diabetes.
  • Sometimes, pregnancies may implant outside the uterus, most commonly in the fallopian tubes. These pregnancies are not viable due to growth restriction and can threaten the mother’s life if they cause the fallopian tubes to rupture. Women over 40 are at the highest risk of having an ectopic pregnancy when compared to women in other demographics.

Birth Defects

Birth defects are most often caused by genetic abnormalities in the egg that becomes fertilized. As we stated previously, these genetic abnormalities become more common in a woman’s eggs as she gets older.

The most common types of genetic abnormalities affect chromosomes. Normally, babies are born with two copies of each chromosome and when a baby is born with too many or too few chromosomes, they may develop health problems, such as learning disabilities or structural defects in the organs.

Down Syndrome, caused by an extra copy of chromosome 21 (known as trisomy 21), is one of the most well-known genetic birth defects. Mothers over the age of 40 are significantly more likely to give birth to a baby with Down Syndrome. By the age of 40, your odds of giving birth to a baby with Down syndrome are 1 in 70 by age 45, the odds increase to 1 in 19.

Treatments

Your age — alongside other factors, such as your overall health and fertility — may affect whether or not you are able to get pregnant naturally. Whether you are in your 20s and looking to conserve your fertility or in your 30s or 40s trying to get pregnant with the help of assisted reproductive technology, here are some treatments to consider.

Egg Freezing

Medically-speaking, the optimal time to have a baby is in your early 20s. However, many women are not ready to conceive until much later in life. If you are approaching 35 and are not ready to have a baby, or have a progressive health condition that may impact your fertility as you age, you may consider freezing your eggs to be fertilized later on. Egg freezing can improve your odds of pregnancy later in life, but it is also an expensive, invasive procedure that may cause side effects. Your doctor can advise you if freezing your eggs may be the right decision for you.

In-Vitro Fertilization

Women who are struggling to get pregnant naturally may have success with in-vitro fertilization (IVF), either with their own eggs or with eggs from a donor. The process can be expensive and tiresome, but many women in their 30s and 40s have success with IVF.

Furthermore, using donor eggs in IVF can improve your odds of pregnancy significantly if you are an older mother. That being said, many women prefer to try other methods before turning to IVF. The Mira fertility tracker may help you get pregnant naturally by helping you pinpoint the exact date of ovulation, through measuring your fertility hormone concentrations.

Lifestyle Changes

Every woman is born with a finite amount of eggs and as you age the quality and quantity of your eggs decrease, making it more difficult to get pregnant. Fortunately, a healthy lifestyle can help prevent some of the things that can impede pregnancy: obesity, underweight, stress, high blood pressure, and malnutrition. The key takeaway is that staying healthy maximizes your chance of a successful pregnancy, but won’t cancel out the effects of aging on the reproductive system.


Pregnancy after 35: What are the risks?

The trend toward older parenthood looks set to continue, with more women in their 30s having babies now than women in their 20s. Are there more risks involved with pregnancy and birth as maternal age rises? We check out the most recent evidence.

Share on Pinterest More people are having children in their 30s and above, but what are the risks that older parenthood presents?

Recent preliminary data from the Centers for Disease Control and Prevention (CDC) indicate that in 2016, for the first time in three decades, birth rates among women aged 30 to 34 surpassed those among women aged 25 to 29 in the United States.

The average age that women are having their first child is currently at around 28 years of age, up from 26.4 in 2015 , and 26.3 in 2014. Experts often focus on average or mean maternal age due to the birth outcomes that are associated with the age of the mother, such as multiple births and congenital disabilities.

Studies report that people may delay parenthood until 35 or older for a number of reasons.

These reasons include women reaching higher education levels, establishing their career, improved methods of contraception, social and cultural shifts that have left women feeling not ready to have children, lack of childcare, low benefit levels, inflexible workplace policies, economic or housing uncertainty, and unemployment.

Another reason why women are going through pregnancy later in life could be down to improved fertility options, such as IVF.

Pregnant women over the age of 35 and having their first baby have been termed as being advanced maternal age (AMA) or older mothers, or they are being referred to as an elderly primigravida or elderly primipara. The terms “advanced age” and “elderly” have negative connotations for someone of just 35 years. Are these terms unfounded, or does being over 35 pose a serious risk for the mother and baby?

Share on Pinterest Fertility declines in both men and women with age.

Everyone is aware of the ticking of the biological clock, but does your 35th birthday represent a particularly special milestone in biology? Do you hit 35 and suddenly become “high risk” overnight?

Women are delivering healthy babies throughout their 30s and beyond. The age of 35 is simply an age that certain risks become more worthy of discussion.

While these risks become slightly more likely after hitting 35 years old, this does not mean that they will have a significant impact on everyone in their mid-thirties and older.

Decline in fertility

Women are born with all the eggs they will ever have. As females age, the likelihood that they will get pregnant reduces due to the declining number of remaining eggs and their reduced quality.

Fertility also declines in men with age due to declining sperm counts, motility, and semen volume. These age-related factors combined can make it more difficult for women to become pregnant.

One study , published in The New England Journal of Medicine, found that among women who received artificial insemination, 74 percent of those under 31 years old were pregnant within a year. However, this decreased to 61 percent of individuals between the ages of 31 to 34, and it further declined to 54 percent of women aged 35 and over.

Genetic risks

Certain genetic risks present more often in pregnancy as women age. For example, the rate of having a baby with Down syndrome accelerates with maternal age.

While the rate of an embryo having Down syndrome at the 10-week mark of pregnancy is 1 in 1,064 at age 25, this rises to 1 in 686 at age 30 and 1 in 240 by the age of 35 years. At the age of 40, the Down syndrome rate increases still to 1 in 53, and down to 1 in 19 embryos at age 45.

A study published in Nature Communications set out to investigate why older mothers have a heightened risk of giving birth to children with congenital anomalies that are characterized by abnormal chromosome numbers.

Researchers from the Albert Einstein College of Medicine of Yeshiva University in New York learned that the genetic process of recombination could be responsible for the increased risk of conditions such as Down syndrome.

Recombination is the process in which pairs of chromosomes exchange genetic material before separating. The team found that in older mothers, the process of recombination may be less regulated, which may lead to abnormal chromosome numbers in sex cells or large chromosomal rearrangements.

Miscarriage

The risk of miscarriage climbs gradually with the mother’s age. Research published in the BMJ showed that risk of miscarriage is around 8.9 percent for women aged 20 to 24 years and increases to 74.7 percent for individuals aged 45 years or above. The declining quality of women’s eggs is thought to be responsible for the higher rates of miscarriage.

Stillbirth

Stillbirth is more likely in older women than younger women. A systematic review published in the Canadian Medical Association Journal found that stillbirth is around 1.2 to 2.23 times higher in older women.

Another study , examining data from 385,120 pregnancies in the United Kingdom, observed that the rate of stillbirth was 4.7 per 1,000 for women aged 18 to 34, 6.1 per 1,000 between the ages of 35 and 40 years, and 8.1 per 1,000 for women aged 40 and over.

Furthermore, the stillbirth rate has been shown to be higher in people having their first child and even higher in first-time moms aged 35 or older.

Women aged 35 years and older are often recommended to be induced as they approach their due date because of the increasing risk of stillbirth with gestational age. Around 1 in 1,000 women under 35 years old have a stillbirth during 39 and 40 weeks of gestation, compared with 1.4 in 1,000 women aged 35 to 39, and 2 in 1,000 women at age 40 and above.

The reasons that stillbirth rates increase with maternal age are currently unclear.

Other risks

Research comparing pregnancy complications among women aged 18 to 34 years, 35 to 40 years, and 40 and over, found small increases in most pregnancy- and birth-related complications with age.

Share on Pinterest Birthing outcomes such as emergency cesarean delivery and postpartum hemorrhage are increased with maternal age.

The researchers identified increases in the risk of gestational diabetes, placenta previa, breech positioning of the baby, emergency cesarean delivery, postpartum hemorrhage, preterm birth, low birth weight, and high birth weight. Other research has found that risk of maternal mortality also increases with age.

Research presented at the American Stroke Association’s International Stroke Conference 2016 revealed that compared with women who go through pregnancy at a younger age, pregnant women aged 40 and older are at greater risk of ischemic stroke, hemorrhagic stroke, heart attack, and death from cardiovascular disease.

“We already knew that older women were more likely than younger women to experience health problems during their pregnancy,” said Dr. Adnan I. Qureshi, director of the Zeenat Qureshi Stroke Institute in St. Cloud, MN. “Now, we know that the consequences of that later pregnancy stretch years into the future.”

Dr. Qureshi and colleagues found that all the risks, except for hemorrhagic stroke, were explained by well-known risk factors for cardiovascular disease – such as high blood pressure, diabetes, and high cholesterol – that older pregnant women face.

Recent research published in The Journal of Physiology sheds light on why women over 35 years old are more likely to face birth complications. Researchers from King’s College London in the U.K. discovered, in a mouse model, that a mother’s age influences the structure of the uterus.

In a group of mice that represented women over 35 years old, muscle contraction properties in the uterus were found to be impaired, less sensitive to oxytocin, and have reduced mitochondria numbers, all of which suggest that the uterus muscles are less able to contract properly. Furthermore, researchers found changes in progesterone signaling, which triggered a delay in labor.

“Our research highlights that there are key physiological and cellular changes associated with a mother’s age that result in labor dysfunction,” explained Dr. Rachel M. Tribe, lead investigator of the study at King’s College London. “Timing of delivery and progress of labor is directly related to maternal age, and this can cause complications during birth.”

Babies who are born at a low birth weight often have more respiratory, cognitive, and neurological problems, while preterm babies are more likely to have heart defects, brain damage, lung disorders, and delayed development.

Some studies have indicated that there is an elevated risk of low birth weight (under 2.5 kilograms) and preterm birth (before 37 weeks of pregnancy) for women aged 35 or older. However, a recent study – conducted by Mikko Myrskylä, director of the Max Planck Institute for Demographic Research, and Alice Goisis, from the London School of Economics in the U.K. – suggests that a mother’s age is not the reason.

The research, published in the American Journal of Epidemiology, found that the reasons are more likely to be associated with individual circumstances or behaviors that are more common in older adults.

Potential candidates for these factors could be fertility problems, which are connected with poor birth outcomes, maternal stress, and unhealthy behaviors.

“Our findings suggest that women should not be concerned about their age per se when considering to have a child,” said Myrskylä. “It seems that individual life circumstances and behavioral choices are more important than age.”

People deciding whether to postpone parenthood should take into account declining fertility and increases in the risk of miscarriage and birth complications. Stillbirths are relatively rare, but the risk remains higher for older women than their younger counterparts and increases in the final weeks of pregnancy.

There are, of course, many plus points of putting off motherhood until after age 35. Children of older mothers have been found to have fewer behavioral, social, and emotional difficulties.

According to another study conducted by Myrskylä and his colleague Kieron Barclay, at the London School of Economics, being born later is also associated with being healthier, taller, and obtaining more education.

“ The benefits associated with being born in a later year outweigh the individual risk factors arising from being born to an older mother. We need to develop a different perspective on advanced maternal age. Expectant parents are typically well aware of the risks associated with late pregnancy, but they are less aware of the positive effects.”

Mikko Myrskylä

Despite the risks, most women aged 35 and older will have a normal pregnancy with few birth complications, and go on to deliver a healthy baby.


How do chromosomes work?

To understand the connection between a woman’s age and potential chromosomal abnormalities in her children, let’s reach back to high school Human Biology.

Everyone has 23 pairs of chromosomes in most cells in the body. The exceptions are eggs and sperm. Chromosomes carry DNA, the genetic information that determines everything about us. Each chromosome is made up of two sister strands of DNA.

As mentioned above, women are born with their eggs already present in their ovaries. At birth, the chromosomes within those eggs are paused in the process of dividing. Division resumes during ovulation and is completed when the egg is fertilized by a sperm cell.

In the initial division, each pair of chromosomes within the egg separates into single chromosomes. During the second round of division, the individual sister strands of each single chromosome separate. The central portion of the chromosome plays an extremely important role in the equitable division of the chromosomes.

The egg must go from having 23 pairs of chromosomes (46 total chromosomes) down to having just 23 single chromosomes. This is so that when the egg and sperm join together, they produce an embryo whose cells each contain 46 chromosomes.

If the division of the chromosomes is uneven, after fertilization the resulting embryo may have one fewer chromosome than normal (monosomy) or an extra copy (trisomy).


The following data is from a recent Thai study of maternal age and trisomies. ⎗]

Genetic Risk Maternal Age
Age of Mother Risk of Trisomy 21 Risk of Any Autosomal Trisomies
Genetic Risk Maternal Age
Age of Mother Risk of Trisomy 21 Risk of Any Autosomal Trisomies
34 2.67 in 1,000 4.54 in 1,000
48 71.06 in 1,000 99.65 in 1,000
Thai study of maternal age and trisomies. ⎗]


Etiology and Clinical Manifestations

Down syndrome is usually identified soon after birth by a characteristic pattern of dysmorphic features (Table 1) .3 , 4 The diagnosis is confirmed by karyotype analysis. Trisomy 21 is present in 95 percent of persons with Down syndrome. Mosaicism, a mixture of normal diploid and trisomy 21 cells, occurs in 2 percent. The remaining 3 percent have a Robertsonian translocation in which all or part of an extra chromosome 21 is fused with another chromosome. Most chromosome-21 translocations are sporadic. However, some are inherited from a parent who carries the translocation balanced by a chromosome deletion.1 , 3 , 4

Frequency of Dysmorphic Signs in Neonates with Trisomy 21

Hyperflexibility of large joints

Loose skin on back of neck

Slanted palpebral fissures

Dysmorphic pelvis on radiographs

Hypoplasia of small finger, middle phalanx

Information from references 3 and 4 .

Frequency of Dysmorphic Signs in Neonates with Trisomy 21

Hyperflexibility of large joints

Loose skin on back of neck

Slanted palpebral fissures

Dysmorphic pelvis on radiographs

Hypoplasia of small finger, middle phalanx

Information from references 3 and 4 .

Molecular genetic studies reveal that 95 percent of occurrences of trisomy 21 result from nondisjunction during meiotic division of the primary oocyte.1 The exact mechanism for this meiotic error remains unknown. Most trisomy 21 pregnancies prove to be nonviable. Only one quarter of fetuses with trisomy 21 survive to term.4

Persons with Down syndrome usually have mild to moderate mental retardation. In some, mental retardation can be severe. School-aged children with Down syndrome often have difficulty with language, communication and problem-solving skills. Adults with Down syndrome have a high prevalence of early Alzheimer's disease, further impairing cognitive function.1

A number of congenital malformations and acquired diseases occur with increased frequency in persons with Down syndrome (Table 2) .1 , 3 – 6 Congenital heart disease and pneumonia are leading causes of mortality, especially in early childhood.

Incidence of Some Associated Medical Complications in Persons with Down Syndrome

Congenital heart defects (atrioventricular canal defect, ventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot)

Hearing loss (related to otitis media with effusion or sensorineural)

Ophthalmic disorders (congenital cataracts, glaucoma, strabismus)

Gastrointestinal malformations (duodenal atresia, Hirschsprung disease)

Atlantoaxial subluxation with spinal cord compression

Increased susceptibility to infection (pneumonia, otitis media, sinusitis, pharyngitis, periodontal disease)

> 99% in men anovulation in 30% of women

Information from reference 1 and 3 through 6 .

Incidence of Some Associated Medical Complications in Persons with Down Syndrome

Congenital heart defects (atrioventricular canal defect, ventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot)

Hearing loss (related to otitis media with effusion or sensorineural)

Ophthalmic disorders (congenital cataracts, glaucoma, strabismus)

Gastrointestinal malformations (duodenal atresia, Hirschsprung disease)

Atlantoaxial subluxation with spinal cord compression

Increased susceptibility to infection (pneumonia, otitis media, sinusitis, pharyngitis, periodontal disease)

> 99% in men anovulation in 30% of women

Information from reference 1 and 3 through 6 .


IVF – In Vitro Fertilization

In Vitro Fertilization is an assisted reproductive technology (ART) commonly referred to as IVF. IVF is the process of fertilization by extracting eggs, retrieving a sperm sample, and then manually combining an egg and sperm in a laboratory dish. The embryo(s) is then transferred to the uterus. Other forms of ART include gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT).

Why is IVF used?

IVF can be used to treat infertility in the following patients:

  • Blocked or damaged fallopian tubes including decreased sperm count or sperm motility
  • Women with ovulation disorders, premature ovarian failure, uterine fibroids
  • Women who have had their fallopian tubes removed
  • Individuals with a genetic disorder
  • Unexplained infertility

How is In Vitro Fertilization Done?

There are five basic steps in the IVF and embryo transfer process:

Step 1: Fertility medications are prescribed to stimulate egg production. Multiple eggs are desired because some eggs will not develop or fertilize after retrieval. A transvaginal ultrasound is used to examine the ovaries, and blood test samples are taken to check hormone levels.

Step 2: Eggs are retrieved through a minor surgical procedure that uses ultrasound imaging to guide a hollow needle through the pelvic cavity to remove the eggs. Medication is provided to reduce and remove potential discomfort.

Step 3: The male is asked to produce a sample of sperm, which is prepared for combining with the eggs.

Step 4: In a process called insemination, the sperm and eggs are mixed together and stored in a laboratory dish to encourage fertilization. In some cases where there is a lower probability of fertilization, intracytoplasmic sperm injection (ICSI) may be used. Through this procedure, a single sperm is injected directly into the egg in an attempt to achieve fertilization. The eggs are monitored to confirm that fertilization and cell division are taking place. Once this occurs, the fertilized eggs are considered embryos.

Step 5: The embryos are usually transferred into the woman’s uterus three to five days following egg retrieval and fertilization. A catheter or small tube is inserted into the uterus to transfer the embryos. This procedure is painless for most women, although some may experience mild cramping. If the procedure is successful, implantation typically occurs around six to ten days following egg retrieval.

How Successful is IVF?

The success rate depends on a number of factors including reproductive history, maternal age, the cause of infertility, and lifestyle factors. It is also important to understand that pregnancy rates are not the same as live birth rates. In the United States, the live birth rate for each IVF cycle started is approximate:

  • 41-43% for women under age 35
  • 33-36% for women ages 35 to 37
  • 23-27% for women ages 38 to 40
  • 13-18% for women ages over 40

Are There Any Side Effects?

Although you may need to take it easy after the procedure, most women can resume normal activities the following day.

Some side effects after IVF may include:

  • Passing a small amount of fluid (may be clear or blood-tinged) after the procedure
  • Mild cramping
  • Mild bloating
  • Breast tenderness

If you experience any of the following symptoms, call your doctor immediately:

Some side effects of fertility medications may include:

  • Headaches
  • Mood swings
  • Abdominal pain
  • Hot flashes
  • Abdominal bloating
  • RARE: Ovarian hyperstimulation syndrome (OHSS)

Are There Any Risks?

As with most medical procedures, there are potential risks. More severe symptoms, typically from OHSS, include the following:

    or vomiting
  • Decreased urinary frequency
  • Shortness of breath
  • Faintness
  • Severe stomach pains and bloating
  • Ten-pound weight gain within three to five days

If you experience any of these symptoms above, contact your doctor right away. Additional risks of IVF include the following:

  • Egg retrieval carries risks of bleeding, infection, and damage to the bowel or bladder.
  • The chance of a multiples pregnancy is increased with the use of fertility treatment. There are additional risks and concerns related to multiples during pregnancy including the increased risk of premature delivery and low birth weight.
  • Though the rates of miscarriage are similar to unassisted conception, the risk does increase with maternal age.
  • The Mayo Clinic reports that the risk of ectopic pregnancy with IVF is 2-5%. An ectopic pregnancy is when a fertilized egg implants anywhere outside the uterus and is not viable.
  • Assisted reproductive technology (ART) involves a significant physical, financial, and emotional commitment on the part of a couple. Psychological stress and emotional problems are common, especially if in vitro fertilization (IVF) is unsuccessful.
  • IVF is expensive, and many insurance plans do not provide coverage for fertility treatment. The cost for a single IVF cycle can range from at least $12,000-$17,000.

What if I don’t produce healthy eggs or my husband is sterile?

You may choose to use donor eggs, sperm, or embryos. However, make sure to talk with a counselor experienced with donor issues. You will want to be informed about various legal issues related to gamete donation including the legal rights of the donor.

How many embryos should be created or transferred?

The number of embryos transferred typically depends on the number of eggs collected and maternal age. As the rate of implantation decreases as women age, more eggs may be implanted depending on age to increase the likelihood of implantation. However, a greater number of eggs transferred increases the chances of having a multiples pregnancy. Make sure to talk with your doctor before the procedure so you both agree on how many embryos to implant.

How do I choose an infertility clinic?

There are a number of questions to ask regarding the cost and details of specific centers and fertility programs. Some suggested questions are available online in Selecting Your ART Program. Some couples want to explore more traditional or over the counter efforts before exploring infertility procedures. If you are trying to get pregnant and looking for resources to support your efforts, we invite you to check out the fertility product and resource guide provided by our corporate sponsor. Review resource guide here.

Want to Know More?

  • How to Get and Keep a Healthy Sperm Count
  • Infertility 101: What You Need to Know First
  • Fertility Friendly Lubricants
  • Ovulation: Frequently Asked Questions

Compiled using information from the following sources:

1. American Society for Reproductive Medicine. (2014). Gamete and embryo donation: Deciding whether to tell.

2. Human Fertilisation & Embryology Authority. (2014). IVF – What is in vitro fertilization (IVF) and how does it work?

3. Human Fertilisation & Embryology Authority. (2014). Risks of fertility treatment.


Age and the Risk of Miscarriage

As women, we hear a lot about the difficulty of getting pregnant as we age, but staying pregnant can often be the bigger challenge, especially as our fertility begins to wane.

The risk of miscarriage rises as a woman ages, with a dramatic rise starting after age 37, with the steepest increase occurring after age 40. By age 45, less than 20% of all recognized pregnancies are viable.

The man’s age matters too. Having a partner over the age of 40 significantly raises the chances of a miscarriage.

Over half of miscarriages are caused by genetic abnormalities. As women age, chromosomal defects in their eggs become increasingly common. On average, a woman in her early 20s will have chromosomal abnormalities in about 17% of her eggs this percentage jumps to nearly 80% by a woman’s early 40s. And as men age, chromosomal defects and point mutations–changes to a single nucleotide in their DNA–become increasingly common.

How The Chances of Miscarriage Vary By Age

Anne-Marie Nybo Anderson, of the Danish Epidemiology Science Centre, led the largest population-based study ever conducted on age and miscarriage. She tracked every “reproductive outcome”–pregnancies, miscarriages, births, stillbirths, and induced abortions– from a total of over a million pregnancies.

The risk of pregnancy loss rose sharply by a woman’s late 30s and reached nearly 100% by age 45.

Most of the rise in fetal losses came from an increase in miscarriage. However, rates of ectopic pregnancy also rise considerably with age:

Somewhat reassuringly, while stillbirth risk increases after a woman’s late 30s, it remains less than 1% through age 45.

Anderson’s study’s findings are similar to another well-studied sample, that of U.S. pregnancies conceived via IVF:

As you can see, the overall risk of miscarriage for IVF pregnancies in the US is slightly lower than that shown in the Denmark sample.

While IVF helps many couples overcome their fertility problems, it largely cannot overcome the age-related increase in genetic abnormalities. Without genetically normal sperm and eggs, a viable pregnancy is impossible.

The lower miscarriage rate is instead due to selection effects. The miscarriage rates are only from women who successfully manage to become pregnant through IVF, a select group. Not all women who undergo IVF have a successful egg retrieval. And of those eggs , not all will develop normally. The embryos ultimately transferred are chosen based on early signs of normal development, raising the odds of an ongoing pregnancy.

Men‘s Age and The Chances of Miscarriage

Most studies on miscarriage only consider the woman’s age on miscarriage, utterly ignoring any influence of her partner’s age.

This is not because of sexism. Instead, the reasons are largely practical: Women tend to marry men who are about their age, so it is hard to separate the risks of a woman’s age from the risks of her partner’s age they are too confounded.

Despite this problem, several studies involving couples discordant for age now paint a clear and consistent picture: older prospective fathers raise the risk of miscarriage by about 25-50%. One study found an a 60% increase in the odds of a miscarriage if the father was over 40. Another found a roughly 25% increase in the risk of miscarriage for fathers over the age of 35.

Other studies report similar effects all finding that the risk rises most markedly for men over 40 (see here and here ).

Men and Women’s Combined Age

Having a young partner may offset some of the risk associated with being older, for both men and women. Men whose partners are young, under 30, appear to have relatively low chances of miscarriage regardless of their own age, according to a large retrospective European study .

For women, though, having a young partner does not erase the effect of their own age. Women over 35 with relatively young partners, under 40, faced double to triple the odds of miscarriage compared to women under 30.

For women in their 30s, having a younger partner lowers the chances of a miscarriage. Compared to a women in her early 30s with a partner of the same age or younger, a woman in her early 30 with a partner over 40 has roughly triple odds of a miscarriage. A woman over 35 with a partner over 40 has four times the odds of miscarriage.

Risk of Miscarriage After Confirmation of a Fetal Heartbeat

On a more positive note, women in their late 30s and early 40s have a good chance of a continuing pregnancy once a fetal heartbeat has been confirmed.

After confirmation of a heartbeat at 7-10 weeks, the risk of a subsequent miscarriage for women over 40 drops to about 10%. After 20 weeks, the risk of a pregnancy loss is less than 1%.

The Bottom Line

The risk of miscarriage rises substantially with age, especially after age 40, for both men and women. Couples may suffer from the compound effect of their ages. Once a pregnancy is past the first trimester, however, the odds of a miscarriage are low, even for older couples.



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