John S. Rinehart

Article / Updated 05-11-2022

Women’s infertility issues can be very complex because so many different systems can be at fault. Is the problem uterine, tubal, hormonal, age-related, or ovarian? Any one of these problems can cause enough trouble to prevent you from becoming and staying pregnant. A healthy uterus Maybe you had an HSG to evaluate your fallopian tubes and uterus, or maybe you had a hysteroscopic surgery for an even closer look into the uterus. Looking at the uterus is an integral part of any fertility workup because the uterus nourishes and holds a baby for nine months. Finding fibroids in the uterus Fibroids, or benign tumors, are commonly found inside or on the outside of the uterus. They’re extremely common, with 40 percent of women between the ages of 35 and 55 having at least one. Fibroids are even more common in African-American women, with 50 percent having at least one. Fibroids can cause bowel or bladder problems, very heavy bleeding, or pain. Fibroids can be either inside or outside the uterine cavity; their location determines whether they cause a problem with your ability to get or stay pregnant. Fibroids completely outside the uterus, such as pedunculated fibroids, which are attached to the uterus by a stem, don’t usually cause a problem with fertility. Submucosal fibroids grow through the lining of uterine wall and can cause a miscarriage. Fibroids can be surgically removed through a process called a myomectomy. A small fibroid inside the uterus can usually be removed by hysteroscopy, a procedure in which a thin telescope is inserted into the uterus through the vagina. This is outpatient surgery and is relatively atraumatic. In contrast, large intramural fibroids require an abdominal incision and a hospital stay. You generally need to deliver by cesarean section after an abdominal myomectomy. Removing polyps in uterus Polyps are small fleshy benign growths found on the surface of the endometrium. Very small polyps usually cause no problem with getting pregnant, but larger polyps or multiple polyps can interfere with conception. Polyps can cause irregular bleeding; they can be diagnosed via sonohysterogram or hysteroscopy and can be scraped off the endometrium. Polyp removal is called polypectomy. Clearing out the fallopian tubes Most women have two fallopian tubes, one on each side of the uterus, next to the ovaries. Because these tubes are the transport path from the ovary to the uterus, a problem with one or both tubes can have a big impact on your baby-making ability. How fallopian tubes should work and what can go wrong Fallopian tubes are not just tubes. If they were, then repair would be much simpler and far more successful. Tubes actually have jobs to do: specifically, to transport and culture. The tube is where the sperm and eggs meet, and fertilization takes place. So, the tube must allow sperm to migrate through the uterus and into the tube. The tube also must pick the oocyte from the surface of the ovary when it is ovulated and move it nearer the uterus. Finally, once the fertilized egg, now called an embryo, has developed for two to three days, the tube must move the embryo into the uterus. The inside of the tube is lined with cells that have hair-like projections that move in a wave-like fashion to transport the embryo. (Think beach ball at a football game moving around the crowd.) Infections can damage these hair-like projections and decrease or destroy the tube’s ability to perform the transport function. This is a microscopic function and therefore cannot be diagnosed. Also, the tube acts as an incubator for the early development of the embryo. The environment in the tube, designed specifically for the embryo, is unlike anywhere else in the body. This function also cannot be seen or diagnosed. Sometimes a tube is surgically removed after an ectopic pregnancy, a pregnancy that starts to grow in the tube rather than in the uterus. If this pregnancy is found early enough, it may be possible to dissolve the pregnancy with a chemotherapy agent called methotrexate. However, if the fetus grows large enough undetected in the tube, the tube can burst, causing life-threatening bleeding. The only way to stop the bleeding is to remove the tube. You can get pregnant with only one tube but having one ectopic pregnancy leaves you at a higher risk to have another. Frequently, when a tube is removed, the surgeon will look at the other tube and find that it looks okay. For a person with an ectopic and one remaining tube, the pregnancy rate is estimated to be about 70 percent, of which 10 percent are another ectopic. So why don’t the other 30 percent conceive? Probably because the tube may appear normal and be open, but damage on the interior of the tube has caused it to malfunction and not be able to perform the job it needs to do. When women become pregnant after an ectopic has been removed, they usually do so within the first year. Beyond that pregnancies can occur but they are rare, and the couple may want to pursue IVF. Damaged tubes Women who have only the left ovary and the right fallopian tube can get pregnant because the egg can “float” to the remaining tube. Of course, this also applies to women who have the left tube and the right ovary. (One study estimated that the egg gets picked up by the opposite tube about 30 percent of the time.) Sometimes fallopian tubes are seen to be enlarged on ultrasound or during an HSG. If the tubes are very swollen and dye doesn’t flow through them, you may have a hydrosalpinx, the medical term for a tube filled with fluid. If both tubes are dilated, the condition is known as hydrosalpinges. A hydrosalpinx interferes with pregnancy in two ways: The egg cannot be picked up by the dilated tube, whose fimbriae (the end) is blocked by scarring. The tube has an environment that damages the development of the embryo. The treatment for a hydrosalpinx is surgical. In mild cases, the end of the tube can be opened and the ends peeled back like a flower. Surgical repair of damaged tubes has a low chance of success primarily because surgical repair does not address the damage on the interior of the tube. However, in severe cases, the tube will not work even if it is opened. In these cases, the tube or tubes must be removed, and you need to have IVF. This diagnosis is a hard thing for many women to accept because it definitely ends any chance that they’ll be able to get pregnant on their own. However, well-done studies have demonstrated that pregnancy rates are lower for women with bilateral hydrosalpinges. Having one hydrosalpinx and one open tube still reduces the chance for a successful IVF cycle. The reason why the hydrosalpinx reduces the pregnancy rate is unknown, but theories propose that the fluid in the tube can leak into the uterus prevent implantation. In very rare cases, women can be born without any fallopian tubes; often the tubes are missing as part of a syndrome in which the external sex organs look normal, but the vagina, uterus, and fallopian tubes are missing. Of course, if you’ve had two ectopic pregnancies, you may have had both tubes surgically removed also. Sometimes fallopian tubes look fine on an X-ray but may be surrounded by adhesions (scarring) that prevent them from picking up the egg. Endometriosis, tissue growths found anywhere in the pelvis, can grow in or around the fallopian tubes and is a common cause of adhesions around tubes. Normal tubes can’t be visualized by ultrasound. Because the fallopian tubes play such a large role in getting pregnant, you’ll probably need intervention, such as IVF, to get pregnant if a problem is discovered with them. Removal or absence of the tubes, or a blockage that can’t be removed, makes IVF inevitable if you’re trying to get pregnant. Addressing scar tissue For doctors who perform surgeries in this area, it's typical to see scar tissue, or adhesions (as shown), in your reproductive system. Many women having a second or third cesarean section delivery or other surgery had scar tissue throughout the pelvis that needed to be cut away before the delivery team could get to the uterus. Adhesions form when blood and plasma from trauma, such as surgery (like an appendectomy, tubal removal of an ectopic pregnancy or fibroid), form fibrin deposits, which are threadlike strands that can bind one organ to another. They can be removed, but surgery to correct adhesions may result in — you guessed it — more adhesions. The amount of scarring depends upon the surgical procedure done but can occasionally be extensive. Adhesions can cause pelvic pain; cesarean sections can cause adhesions, but they tend to be anterior (or in front of) the uterus, and thus may cause difficulty during a subsequent C-section. However, C-sections don’t usually cause problems with tubes (which tend to be behind the uterus), and thus don’t usually cause infertility. Your chances of getting pregnant after adhesion removal are highest in the first six months after surgery, before extensive adhesions form again. Some adhesions can’t be removed without damaging the tubes or ovaries, and you may need IVF to get pregnant. Since the advent of IVF, surgical repair for pelvic adhesions is uncommon. If you have adhesions in the uterus itself, you may be diagnosed with Asherman’s syndrome, also called uterine synechiae. Asherman’s can follow a dilation and curettage (D&C), an abortion, or a uterine infection. It can be diagnosed during an HSG but is best diagnosed with a hysteroscopy, where the inside of the uterus can be visualized. Asherman’s is also suspected if you have scant or no menstrual flow or recurrent miscarriages following uterine trauma. There are varying amounts of scarring in Asherman’s syndrome. Some people have very few adhesions, and these are filmy and easy to remove. That person has a very good chance to conceive. If the mild to moderate adhesions are removed surgically, you have a good chance, probably 75 percent or better, of becoming pregnant and carrying to term. Severe adhesions may destroy nearly all the normal uterine lining, and pregnancy may not be possible. Less frequently, a person will have extensive intrauterine scarring and that person will have a very poor chance for achieving a pregnancy. A gestational surrogate may be needed in these cases.

Article / Updated 09-02-2021

How exactly do genes work, and why are they important if you are trying to have a baby? Nothing is more popular around the dinner table than crediting or blaming your family for who you are. You are so good at math — just like your dad. You sing like a dream — just like your mom. Always late like your Aunt Ellen! Grandma’s eyes, Grandpa’s hair, Aunt Susie’s wit, Uncle Bert’s moods . . . and your sister’s funny little toe can all be found in you, and it must be because of your genes. Grasping genetics basics Genetics has become a very popular word. With that popularity has come myth and misunderstanding. But the concept of the field of genetics is really quite simple. Genetics deals with the instruction manual on how to build a human. To be exact, a Google search gave the definition of genetics as “the study of heredity and the variation of inherited characteristics.” One analogy is to view the instructions on how to build a human as a book, passed on from generation to generation, which is called inherited. The book is divided into chapters called chromosomes. The chapters have paragraphs called genes, and the words are made from a very simple alphabet. And just in case you are feeling special, the majority of the book, (99 percent) has the same chapters as the manual for building a chimpanzee. Also, the person you think is, well, “different,” actually has the same 99.9 percent of your genetic code. Reassuringly, given the size of the genetic code, that is still over three million differences. The estimate is that the human genetic code has over 3 billion units, which is huge, but the lowly Amoeba dubia has over 670 billion units. So, it really is not how you say it but what you say that matters. What are genes and chromosomes? Genes are a long string of four chemicals called nucleotides and lettered as A (adenine), C (cytosine), G (guanine), and T (thymine). Words in the code are made from just these four chemicals, and the alphabet has only four letters. That’s really a small alphabet to create a person. The English alphabet has 26 letters, and if you limit the number of syllables a word could have to 14, over 2.75963 x 107 words are possible. Fortunately for those spelling whizzes, the English language has only a little over 200,000 words. The genetic code has only four letters, and the words (codons) can be only three letters long, so at most 64 possible combinations are used for the genetic code. The directions for building a human, the genetic code, is a string of three-letter words. However, the string is not one continuous string but rather 23 strings of code. These 23 separated strings are called chromosomes. Each time a cell wants to divide, it must accurately create two copies of the genetic code, and it does this one word (codon) at a time. To complicate this even further, a person inherits one set of chromosomes from each parent so that each cell has two copies of each chromosome. Thus, inheritance is a demanding task of accurately repeating the copying of the code over and over to create the 37 trillion or so cells that make a human. What do genes do? Genes are used to direct a cell to make proteins. Proteins are strings of molecules called amino acids, and there are 20 that are used to make proteins. Proteins are the workhorse of constructing a human. The DNA uses a different type of genetic material called RNA to assemble proteins from the amino acids. Each gene determines which amino acids are to be used and in what sequence. The way in which the amino acids are strung together determines the three-dimensional structure of the protein. The structure of protein is critical for it to do its job properly. Any error in the sequence of the amino acids may reduce the efficiency of how the protein works or make it completely nonfunctional. Inheriting infertility—really? The construction of a human is immensely complicated. For proper functioning, all of the various parts need to work together. Any part that does not do its job properly can throw the person out of balance and thus create disease. So normal human functioning means that the systems are in equilibrium and working properly together. Any part not functioning in equilibrium causes the disease. The genetic code determines the basis for the equilibrium; any error in the code can cause the person’s equilibrium to be disturbed, and disease follows. For people having problems conceiving, a question that needs to be answered is whether errors in the genetic code are causing the problem of getting pregnant. Infertility and sterility are not the same. Infertility implies that pregnancy is not occurring in the normal time frame. Sterility means that the person will never have her own genetic child. So, when a group of people are diagnosed with infertility, there are actually two groups: one group is sterile, and the other group is subfertile and may achieve a pregnancy on their own or may need help with infertility treatments. There are a number of different types of genetic errors. Sometimes entire chromosomes may be missing or duplicated. There may be deletions of parts of the chromosome or parts that are misplaced or turned around. There can be errors in the letters of the code, thus causing the wrong amino acid to be used. These errors are called single-nucleotide polymorphisms (SNPs). SNPs are the most common form of variation amongst people. The error is the use of the wrong letter such that an A (adenine) is switched to a T(thymine). Most of these will not alter the functioning of the person, but some can cause severe disease such a sickle cell anemia. There are many types of sickle cell disease depending upon the gene mutation, but one form is caused when the sequence GAG is changed to GTG—one single letter can cause the destructive disease. The two most common chromosomal problems causing sterility in females are 47 XXX and 45 X0 (Turner’s syndrome). The 47 XXX syndrome occurs in 1 in 1,000 female births and causes premature ovarian deficiency. Turner’s syndrome occurs in 1 in 2,000 female births. Turner’s syndrome is a disease caused by an entire chromosome being absent. Turner’s syndrome results when a person has only one sex chromosome — an X chromosome. This person develops as a female with characteristics such as short stature, a web neck, and a low hairline, and about one-third will have heart defects. These people do not make eggs, so they are menopausal from birth and thus are sterile. However, some people with this problem have a mixture of cells with some having only one but some having two X chromosomes. This condition is called mosaicism. Depending upon how many cells are normal, this person may display the signs of a person with Turner’s but actually have some eggs. She may be able to have a child, which is rare. Or she may have early normal egg development but run out of eggs very early in life and, thus, lose the ability to have her own child. If this condition is established early, it is possible to harvest some of the eggs and freeze them for later use. A second example of a chromosomal cause of sterility occurs in males. Being a male is determined by the Y-chromosome. A gene on the Y-chromosome directs a man to make sperm. The gene is called the sex-determining region (SRY) and is located on the long arm of the Y chromosome. It is passed unmodified from father to son, and thus any abnormality of the gene will be transmitted to a son. One region of the SRY gene is called the azospermic factor (AZF), and this has three sections termed the a, b, and c regions. Some men with very low sperm counts or with no sperm in the ejaculate have deletions in this region. If a man had a deletion in the “a” region, he will not have sperm and has what is termed Sertoli-only syndrome. That man will not be able to have children that are genetically his. Thus, this type of mutation cannot be inherited. However, if the man has deletions in the “b” or “c” regions, his count may be low or zero but there may be regions of the testes that do make sperm. This man can undergo a testicular biopsy where a very small amount of testicular tissue is removed and tested to see whether sperm are present. If they are, then these can be used in IVF and the man has the possibility for having genetically his own children. If he has a male child, the child will inherit the same deletion as the father, and thus this type of infertility can be inherited. Males can also have impaired fertility or even be sterile if they have too many Y chromosomes. The person is then XYY and has what is called Klinefelter’s syndrome. Some men with this problem do have sperm in the ejaculate and others have sperm which must be extracted from the testes. Unfortunately, some will have no sperm and are thus sterile. Inheriting diseases that may impact fertility—different story! There are genetic causes of infertility that can be passed down from generation to generation, but these usually involve much less of the genetic code. Some are single gene mutations, and some are structural problems with a part of a chromosome being rearranged but not entire chromosome changes. For males, myotonic dystrophy is an inherited disease that is called an autosomal dominant. This means that if the person has the mutation in just one of the chromosomes, he will have the disease. Thus 50 percent of his offspring will also have the disease. The problem is caused by areas of the gene, which produces a protein required for normal functioning, have unwanted repeated sequences of the letters. The general term for this type of problem is nucleotide repeat diseases, and women can have a similar problem causing the fragile X syndrome. Some of these men have sperm and thus can have children, but some will have no sperm and be sterile. Males can inherit genetic diseases affecting fertility that are single gene defect problems. For these, a mutation of many mutations within a gene causes the gene to malfunction. An example of this is cystic fibrosis. A man with cystic fibrosis will have no sperm in the ejaculate because the tubes that transport the sperm from the testicle to the penis (the vas deferens) do not develop. This is called congenital bilateral absences of the vas deferens and can be treated using sperm extraction from the testis and IVF/ICIS. One problem for females that has some genetic basis is polycystic ovary syndrome. No single gene has been identified that causes PCOS. Rather, there are a number of genetic mutations that can cause PCOS. Also, patients with PCOS have DNA that has been modified so that the directions for constructing the human are not read correctly — these modifications are called epigenetic factors. Epigenetic modification of DNA helps explain how the environment can alter the way the genetic code is read, and it plays a major role in a number of diseases. Another type of problem can occur when there are too many copies of a three-letter word, for example egg (a genetic sequence). Fragile X syndrome is an example of this type of genetic error. Fragile X syndrome results when a region of a gene called the FMR1 gene has too many repeated sequences of the genetic word cgg. The FMR1 gene produces a protein that regulates other proteins to make normal nerve connections. The mutation can result in individuals with severe mental compromise. A family with members with severe mental compromise may benefit from genetic testing to determine whether the family has the abnormal FMR1 gene. A normal number of repeats is 5 to 50. If the sequence has more than 200 repeats, then the result is developmental abnormalities in varying degrees. However, where there are 50–200 repeated sequences, the person may have some developmental problems, or a female may have early ovarian failure. So experts often test a woman with premature ovarian failure to determine whether she has too many repeat sequences. There are a number of single gene defects that affect the fertility of a person. These are being diagnosed more and more so the list is becoming quite long. It is beyond the scope of this article to fully explore these diseases. Shaking the family tree for information The fact that genetics is playing a larger role in the cause and potential treatment of all diseases makes knowledge about families important. Doctors are now taking a more extensive family history, and if it seems warranted, they construct a genetic diagram (family tree). Many people have at least one disease-causing genetic mutation if it occurs on both chromosomes. Fortunately, people have two chromosomes, so the mutation does not cause a clinical problem. But if two people have children and they both have the same mutation, then one out of four children may have the disease. A family tree may show relatives that had symptoms of the diseases which would put the couple on alert to test for the mutation.

Article / Updated 09-02-2021

When some fertility test results come back, you may be even more confused than you were before. If your partner’s semen analysis comes back with some results askew, he may be too embarrassed to ask what the results mean. Semen samples can vary from month to month, or even day to day. That’s because it takes about 72 days for sperm to develop. Unlike eggs, which are present from your embryonic days, sperm are replenished all the time. Because men are constantly producing new sperm, one “bad” semen analysis should be followed up with another in a month or so to see if the problem was a temporary one. An illness, injury, or medication or drug used a few months before may make one sample not so superior, but checking again a month later may show an improvement. Making too few sperm Sometimes a semen analysis shows a very low number of sperm, less than 15 million/ml, a condition called oligospermia. While 15 million sperm may sound excessive — why isn’t one or two million enough? — large numbers of sperm are needed in the ejaculate because many sperm are abnormal even in a good sperm sample, and it’s a long way to the ovulated egg, so many don’t make it all the way. There are many causes of oligospermia, ranging from varicoceles to lifestyle issues. Other causes may be Hormone imbalances, which can be checked by a simple blood test Chromosomal abnormalities such as a congenital deletion of part of the Y chromosome History of lymphoma or testicular cancer or chemotherapy Diabetes Sickle cell disease Kidney disease Liver disease You can get pregnant without fertility treatments if your partner has oligospermia, but your chances of pregnancy are higher if you do one of the following: Intrauterine insemination (IUI): The sperm are concentrated and “washed” so that the best sperm are used for insemination. In vitro fertilization (IVF): This treatment allows fertilization to take place in the lab, where a high concentration of sperm can be put in with the egg. If the sperm are especially abnormal, the lab may need to utilize intracytoplasmic sperm injection (ICSI), the insertion of a sperm directly into an egg. The procedure is done by an embryologist under a high-powered microscope. When there’s no sperm in sight If no sperm are seen, it’s called azoospermia. About 1 percent of males have azoospermia. If your partner has azoospermia, you won’t be able to get pregnant conventionally. Different factors can cause azoospermia; either the production of the sperm or the delivery of the sperm can be at fault. Sperm production problems can be caused by the following: Sertoli cell only syndrome: In this condition, the germ cells that produce sperm in the testes are absent. There is no way for a person with this syndrome to father a child. Anabolic steroids: Their use may cause irreversible shutdown of the sperm production. Abnormal hormone levels: Low levels of LH, FSH, or testosterone can cause low sperm production. This problem can be treated with hormone injections, pills, or transdermal patches. If the problem is obstruction, in general, the sperm production is normal, and the sperm simply can’t get to the ejaculatory duct. In these cases, your partner will need a surgical procedure to extract the sperm from the testicle (discussed in the nearby sidebar “If you need a sperm aspiration”). This procedure must be done in conjunction with IVF because the sperm need to be injected directly into the egg. Obstructive problems include the following: Absence of the vas deferens, the tube that delivers sperm to the ejaculatory duct and the prostate Previous vasectomy Previous infection that causes scarring and obstruction of the epididymis Obstruction from prior surgery Mechanical problems with getting the sperm where they need to be include the following: Retrograde ejaculation, in which the majority of the sperm go into the bladder Spinal cord injury that prevents ejaculation Previous injury from trauma Previous injury from surgery, such as hernia surgery A disease such as diabetes Considering the sperm’s shape and movement After checking how many sperm are available, the andrologist will look at what shape the sperm are in and how they are moving — kind of like a test to see if they are “in condition” for conception. The terms you’ll see on the report are the morphology (shape) and the motility (how they swim). Morphology There are hundreds of papers written about the shape of sperm. The concern has to do with the ability of sperm to navigate the female reproductive tract to get to the egg in the fallopian tube at the correct time. There are many barriers to this; the cervix with its protective mucus is the primary obstacle. Putting sperm beyond the cervix through the use of intrauterine insemination is based upon the fact that the cervix keeps many sperm from entering the uterus. So while the cervix can act as a storage place for sperm, it can also prevent sperm from moving forward. The theory is that sperm need a specific shape to get through the cervical mucus (see the following figure). Sperm with an abnormal shape may be filtered and not able to move forward. Both IUI and ICSI correct for this problem. But sperm have another issue. Once they reach the egg, they need to penetrate the shell of the egg. Sperm penetrate the shell by binding to the shell and releasing proteins that digest a pathway through the shell. If the sperm do not have these proteins, you could place a bazillion near the egg and they could not penetrate the shell. In the early days of IVF, before ICSI, sperm and eggs were simply placed in a dish. Fertilization had to be done by normally functioning sperm and eggs. It became apparent that some men had sperm that were incapable of fertilizing an egg, but there was no highly reliable test to determine this before the IVF procedure. That meant that couples could go through IVF only to find out that they had no embryos. One school of thought suggested that the shape of the sperm may give an indication about the ability of the sperm to fertilize an egg. To that end, they developed a very detailed process for determining if a sperm had a shape that suggested that the sperm could fertilize the egg. Originally called the Kruger method, the term strict scrutiny is now used to identify that this detailed methodology is being used to determine the percentage of sperm with the desired shape. Labs vary in what they consider normal, but in general anything < 5 percent is abnormal, from > 4 percent to 14 percent may be an indication of a reduced fertility potential, and above 14 percent is normal. Motility In the sperm world, it’s swim or die. Sperm must traverse the female reproductive tract to get to the egg. Any reduction in motility reduces the number of sperm that even have a chance to get to the egg. Like morphology, a reduced motility may sometimes also indicate that the sperm lack the ability to penetrate the shell of the egg. Normal percentages for motility are > 40 percent motile and 32 percent forwardly motile. Sperm lose their motility if they remain in semen too long, and this is why andrology labs needs the specimen within an hour of collection. Also, cold conditions, such as a cold car seat in the winter, can artificially lower the motility. Another condition that can result in lower motility is the thickness of the semen (viscosity). After ejaculation, semen coagulates just as blood does. Over the next 30–45 minutes, it liquefies. Some men have conditions that create either super thick semen (increased viscosity) or failure to liquefy. Both of these may reduce the fertility potential for the man.

Article / Updated 09-02-2021

All the components of your reproductive tract — the vagina, uterus, ovaries, fallopian tubes, and the glands that orchestrate your hormones — have to work together perfectly for you to be able to get pregnant. Although your menstrual cycle seems simple enough, a lot of things, unfortunately, can go wrong and impact your fertility. Take a spin on the menstrual cycle The hormone-secreting systems work to create your menstrual cycle like this: Menstrual Phase: During menstruation, the old uterine lining breaks down and passes through the vagina as menstrual flow. This process takes three to seven days and is commonly called a “period.” Follicular/Proliferative Phase: On Day 1 of bleeding, the pituitary gland, under influence from the hypothalamus, releases follicle-stimulating hormone (FSH). The rising FSH levels cause the ovaries to rescue the 10 to 20 remaining follicles, called antral follicles, which begin to grow. The cells surrounding each egg secrete a liquid, forming a follicle, a fluid-filled sac. Each follicle contains one immature egg. During the follicular phase, one follicle continues to develop, and the others die. In the ovary, the one egg-containing follicle is growing (in response to FSH and luteinizing hormone (LH), which is also produced by the pituitary), and this growing follicle begins producing estrogen. The estrogen produced by the ovary causes the uterine lining to thicken or proliferate. This is called the proliferative phase of the uterus. The follicular phase and the proliferative phase occur in the first half of the menstrual cycle. One refers to what’s happening in the ovary (follicular phase), and the other refers to what’s happening in the uterus (proliferative phase).One follicle becomes dominant, growing faster than the others. As the dominant follicle grows, it produces more estrogen, which also increases the lining of the uterus. The amount of FSH released decreases, and the smaller follicles stop growing and are reabsorbed. A large amount of LH, called an LH surge, is released from the pituitary gland as the estrogen rises. This makes the egg inside the dominant follicle mature. Ovulation: The follicleopens; the egg is released (ovulation) and is picked up by one of the fallopian tubes. If the egg is joined by sperm, it will continue to travel through the fallopian tube to the uterus. The uterine lining has now developed enough to support embryo implantation, and the endometrial glands of the uterine lining secrete proteins that help guide the embryo to the correct spot. Luteal phase: The leftover part of the follicle, now called the corpus luteum, produces progesterone and some estrogen, which help an embryo implant. If you are not pregnant, the corpus luteum collapses, progesterone and estrogen levels decline, the uterine lining begins to break down, and menstruation begins roughly two weeks after ovulation. The importance of regular periods Do your periods always come every 28 days like clockwork? If they do, you’re a rarity; only one in ten women fall into what we’ve been conditioned to think of as a “normal” menstrual pattern. Most women have cycles 25 to 31 days apart. When your doctor asks you how long your cycles are, he’s asking how many days are between Day 1 of one period and Day 1 of the next period. When he asks how long your period is, he’s asking how many days you bleed. Day 1 of your period is the first day of normal (for you) flow, not the day when you have light or irregular spotting before your period starts. If you are on, or have been on, birth control pills, be sure to note that in charting your menstrual pattern. The pill chemically coordinates your cycle to come at the same time each month (provided you take the pill correctly!). What’s regular for you may not be regular for someone else but having some sort of pattern to your periods is important because it indicates that you’re producing and releasing eggs on a regular basis. But just because a woman is having periods does not give us any further information about egg quality or whether her uterus can support a pregnancy. If your cycles are very long or very irregular, you may not be maturing eggs, you may not have sufficient hormone levels, or there may be other underlying medical issues. The causes of malfunctioning menstrual cycles Although it may seem like your menstrual cycle runs like clockwork, always appearing on the expected day, the likelihood is that at least part of the time, your cycle is out of sync, showing up too early, too late, or not at all, even though you’re not pregnant. Irregular periods not only make it hard to determine when you ovulate, but they can also indicate that your reproductive system is in need of fine-tuning. In this section, we discuss all the ways cycles can get out of sync, what it can mean, and how your doctor may suggest fixing them. Menstrual cycles that don’t fall into the norm can indicate that you’re not ovulating at all or that you’re only ovulating occasionally. An occasional irregular cycle can be brought about by stress; a change in routine, exercise, or eating patterns; or illness, but periods that are “never the same length twice,” consistently shorter than normal or longer than normal, should be evaluated by your doctor. Bleeding too often — short cycles If your cycles are very short — less than 25 days apart on a regular basis, you may be ovulating too soon. Since the period between ovulation and the start of your period should consistently be 14 days, if your periods are short, it usually (but not always — we discuss the alternative in this section) means that you have a short follicular phase, the time between your period and your ovulation. A short follicular phase can mean that the egg is developing in the incorrect time frame. Short follicular phases can occur when your ovarian reserve, the number of eggs you still have in your ovaries, is starting to decrease. It occurs because there is an elevation of the FSH level in the previous cycle, which accelerates the development of the egg. So, a clinical pearl is that short cycles may raise red flags about reduced ovarian reserve. A woman who has traditionally had cycles ranging from 28–32 days and then notices that they have shortened to 26–27 days may be showing signs of reduced ovarian reserve. This is especially true if she is over the age of 35. For quite some time, a lot of emphasis was placed on the second half of the cycle or the luteal phase. If this was shorter than ten days, a diagnosis of luteal phase defect was made and sometimes progesterone was used to try to correct for this. While there may be some controversy about this, recent understanding of how the cycle works has suggested that there may not be a luteal phase defect. The luteal phase is dependent upon the first half of the cycle, the follicular phase. The follicular phase is dependent upon the quality of the egg. So short luteal phases are a product of poor egg quality. Bleeding too infrequently or skipping periods Cycles that are very long, over 35 days apart, can indicate that you’re not ovulating regularly. This can be a factor of excessive exercise, weight change, or other factors, but it can also be caused by polycystic ovary syndrome, or PCOS. PCOS can cause changes in hormone ratios that can be diagnosed by your doctor, as well as physical changes such as excessive hair, weight gain, and acne. Endometriosis, premature ovarian insufficiency, abnormal thyroid levels, or high prolactin levels can also cause irregular or absent periods. Bleeding between periods Bleeding between periods can indicate that something is wrong inside your uterus or that your hormones are out of balance. Some of the things that can go wrong with your uterus to cause irregular bleeding are Cervical irritations or infections: Possible causes of cervical bleeding especially if this occurs after intercourse. Fibroids: Benign growths found in the uterine wall Polyps: Small fleshy growths found on the endometrium, the lining of the uterus, or the cervix Bleeding too heavily (menorrhagia) Bleeding too heavily and passing clots can be “normal” for some women, especially in women who are overweight. Fibroids, PCOS, and irregular periods can be related to heavier-than-normal bleeding. Heavy bleeding can also be a sign of recurrent early miscarriage. Women who bleed heavily every month are at risk for becoming anemic (having a decreased number of red blood cells). Anemia can lead to fatigue and weakness, so heavy periods should be checked out with your doctor. A simple blood test can diagnose anemia. Having scant periods If your period is very light, it could be a normal variant, (in which case, lucky you!) or it could be a sign that your uterine lining isn’t getting as thick as it should. Scant periods are typical if you’re using birth control pills or have just stopped using them, or if your periods have just started. If your lining isn’t thickening properly, you may not be ovulating normally, so seeing your doctor is a good idea. Experiencing painful periods (dysmenorrhea) Up to 40 percent of women experience pain with their periods, called dysmenorrhea. Dysmenorrhea falls into two categories: Primary dysmenorrhea has no other underlying cause besides the release of prostaglandins (chemicals made by cells that have specific functions such as controlling body temperature, stimulating smooth muscle, and influencing heat cycles) in the uterus, which cause uterine contractions. Secondary dysmenorrhea is caused by disease present in addition to the normal release of prostaglandins, such as endometriosis, fibroids, or infection. Because painful periods can be caused by diseases that can interfere with getting pregnant, such as endometriosis, you should always see your doctor if you have painful periods. Dysmenorrhea is the most common symptom of endometriosis, which affects more than 5 million women in North America and may cause infertility in up to 30 to 40 percent of its sufferers. The release of prostaglandins that cause cramping can also cause nausea, diarrhea, and exhaustion, just to make you feel really terrible during your periods. Taking anti-inflammatory medications such as ibuprofen can help with the symptoms.

Article / Updated 09-02-2021

Assuming you know how all your parts work, are you ready to have a baby? Yes? Then it’s time to have sex. No, not right now. (Well, okay, if you must, but proper timing will enhance the chance for pregnancy.) So, it is important to have sex when the timing is right. How do you know when the timing is right? This is more than just mood lighting and foreplay. To get pregnant, you need to be close to ovulation. Recognizing signs of ovulation It normally takes between 10 and 14 days to mature a good egg and release it, so if you have 28- to 30-day cycles, you may ovulate sometime between day 14 and day 16 of your cycle. Shorter cycles have an earlier ovulation day, and longer cycles a later ovulation day. How do you know if you’ve ovulated? Some women experience a sharp pain when they ovulate, called mittelschmertz, or have a vaginal discharge; however, these symptoms are very subjective and are not reliable indicators of ovulation. A more reliable method is correctly using an ovulation predictor kit. That said, you may be able to tell that you’re ovulating in a few simple ways, just by watching the calendar and being observant about your bodily functions. Usually the mucus from your cervix increases around the time of ovulation. It also becomes very thin, clear, and stretchy; you can easily stretch it out a couple of inches. Rising estrogen levels from a developing follicle create this mucus, which is easier for sperm to swim through than your usual thicker mucus and also has an alkaline pH, which helps the sperm live longer. At other times of the month, cervical mucus is acidic. Be sure that you’re not confusing cervical mucus with semen from previous sex or increased secretions from sexual arousal. If you have no objection to feeling around inside your vagina, you’ll also notice that your cervix becomes softer, slightly open, and easier to locate with your fingers when you’re about to ovulate. At other times of the month, the cervix is found farther back in the uterus, feels firmer to the touch, and is tightly closed. About 20 percent of women have pain called mittelschmertz (German for “middle pain”) when they ovulate. The pain seems to be caused by blood and fluid released from the ruptured follicle irritating the tissues around the ovary. Sometimes a small amount of vaginal bleeding occurs with ovulation, too. Some women have headaches around the time of ovulation, and others complain of bloating or breast pain. You’re probably already aware of your personal ovulation indicators, but you may have just never paid much attention to them; just don’t be disappointed if you don’t have these symptoms — that doesn’t mean you are not ovulating! Paying attention to when you ovulate is okay but unnecessary. If a woman has regular cycles every 28–32 days, she will ovulate around midcycle. If the goal is to get pregnant through intercourse, then having intercourse every other day around mid-cycle will maximize the chance of getting pregnant. You can have intercourse more frequently if you want. You do not need to worry that you are having too much intercourse. Men do not improve their chances for conception by storing sperm. They aren’t stored in the man’s body — in fact they die and are removed. Timing and fertility Timing is everything when it comes to getting pregnant. Many women miss the mark month after month because of mistaken ideas about the best time to get pregnant. Sperm and eggs both have a short shelf life; eggs are capable of being fertilized for around 24 hours, and sperm can live up to four days in the proper environment, such as the fluid that fills the fallopian tubes. That means that if you don’t have sex within a few days before ovulation, you’re not going to get pregnant. Many women have been conditioned to believe that ovulation occurs on day 14; they have sex on days 12, 13, or 14 in hopes of hitting the right time. But the most consistent thing about your menstrual cycle should be that ovulation occurs 14 days before your period begins. So, if your cycles are 28 days, you ovulate on day 14. But if your cycles are short, say 25 days, you’re actually ovulating on day 11, and having sex starting on day 12 will be too late to achieve a pregnancy. On the other hand, if your cycles are long, say 34 days, you don’t ovulate until day 20. Having sex on day 14 will be way too early, since sperm don’t live for a week. So, timing sex correctly when you want to get pregnant is dependent on a solid knowledge of when you’re ovulating. Sperm live longer in your body than the egg, so err on the early side when deciding when to start having sex. Every other day is enough, and there is no harm in having extra sperm around. When in doubt, just do it! Conceiving a baby: How sex should work The time is right, the moon is bright, and it’s time to get pregnant. Here’s what needs to happen: It’s near ovulation; an egg is about to release from its follicle. You and your partner become aroused. Your vagina produces secretions that make it easier for the now erect penis to enter the vagina. During the man’s orgasm, several million sperm are forcefully ejaculated into the vagina. As they pass through the cervix into the uterus, the cervical mucus “filters” the sperm so that they’re ready to penetrate an egg. Your egg releases from the follicle and enters one of your fallopian tubes. The sperm swim through the uterus up to the fallopian tubes. The next day your egg meets up with several hundred sperm in the fallopian tube, and the sperm all attach themselves to the egg. One sperm breaks through the outer layer of the egg causing a chemical reaction that makes the egg immediately impenetrable to the rest of the sperm. The genetic material of the egg and sperm combine, and the newly created embryo is moved down the fallopian tube to the uterus. Cells which line the inside of the tube have hair-like projections and create a wave, much like moving a beach ball in the crowd at a football game. The embryo remains in the tube for a couple of days where is develops and then is moved into the uterus. So the tube is both a transporter and an incubator for the developing embryo. The embryo implants in the uterine wall and grows, and you miss your period. You’re pregnant! Congratulations. There is no “best” position for making babies.While some “helpful” books, articles, blogs, and even healthcare providers may tell you that lying on your back for a while or elevating your hips after sex will help you get pregnant, doing so isn’t necessary. Similarly, you may have heard that certain sexual positions may work better than others — not so much. You can choose whatever position during or after sex that is right for you and your partner. How often to have sex When you’re trying to get pregnant, it is important to have intercourse every other day. It is a myth that you can have too much sex. Increased ejaculation may make the sperm count lower, but it does not decrease pregnancy rates. In fact, some men with low counts actually increase the amount of sperm they ejaculate with more frequent ejaculations. When you’re close to ovulating, have sex at least every other day; every day is okay. Most doctors recommend the two days before and the day you ovulate as the best time for conception. Other than that, timing should remain routine so that there are no prolonged periods of abstinence. Infertility can severely decrease the joy of sex and the intimacy that usually accompanies intercourse. Don’t drive yourself crazy with things that don’t matter.

Article / Updated 09-02-2021

If you're trying to get pregnant, you will use a lot of home pregnancy tests (HPTs). They’re widely advertised on TV, depicting a couple excitedly waiting for the good news or a tense woman alone hoping for the happy news that she’s not pregnant. Here's all you need to know about HPTs. The first home tests were available in the 1970s, and everyone probably would have been a little more squeamish about leaving them in the fridge next to the milk if they had known that they contained prepackaged red blood cells. These tests were very sensitive to movement, so you had to put them someplace quiet and leave them alone for a few hours. When you finally peeked into the fridge, you looked for the dark ring at the bottom of the tube — that’s what appeared if you were pregnant. The clumping together of red blood cells if you were pregnant is what formed the ring. All the tests, from the 1920s on, measured hCG (human chorionic gonadotropin), the hormone released by the implantation of the embryo and the growing placenta. The newest tests are very sensitive and are able to detect hCG concentrations of 10, 20, or 25mIU/ml (the smaller the number, the higher the sensitivity), which usually occur about ten days after ovulation or about four days prior to the time you would miss your first period. Even though most tests are accurate a few days before your period is due, a negative test at that time may not be accurate. You may have had a late implantation, or you may have ovulated a day or two after you thought you did. Another test should be done a few days later if your period still hasn’t started. The accuracy of any home pregnancy test depends on how closely you follow the directions, when you ovulated, and the sensitivity of the test. If you test too soon, you may get a false negative. If you are pregnant, the average level of hCG 10 days post ovulation is 25mIU/ml; it is 50mIU/ml 12 days post ovulation, and 100mIU/ml 14 days after you ovulate. Keep in mind that these numbers are averages; your number may be higher or lower and still be perfectly normal. Also, as with LH kits, the concentration of the urine can play a large role in whether or not the test turns positive. Because any positive value is important, using first morning (most concentrated) urine is a good idea. Blood tests measure hCG with much more accuracy, detecting concentrations less than 5mIU/ml. How to use HPTs Home pregnancy tests are available in every drugstore, so if you’re buying in bulk because you’re a compulsive tester, you can hit every grocery store and drugstore in town, and no one will know that you’re compulsive — er, anxious to know! These tests give fast results, usually in two to five minutes. Most tell you to not urinate for four hours before you test so the concentration of the hormone will be high. Some kits suggest that you urinate in a cup and dip the wand into it, and other kits suggest peeing directly on the stick. Some show a positive as a little plus sign; others want you to drag all your friends back in to the bathroom (if you still have any friends left after ovulation) and have them compare the control line to the test line to see whether they match. Usually a positive is indicated by a test line that’s as dark as or darker than the control, and many women drive themselves mad staring at the line trying to determine its exact shade of purple. Some tests now eliminate the “match game” by spelling out, “Yes, you’re pregnant” or some variation if your test is positive. Don’t let the test sit around before looking at it, as some test results will change after an hour or two and will not be accurate. See the following figure for positive and negative results on a home pregnancy test. The following table lists the common brands of home pregnancy tests and the lowest number they claim will register a positive result. Sensitivity is measured in units called mIU, which means milli-International Units per milliliter. Home Pregnancy Test Sensitivity Levels Home Pregnancy Test Lowest Sensitivity Level AimStick Pregnancy Test Strip 20 mIU AccuHome Midstream Pregnancy Test 25 mIU Answer Early Result Pregnancy Test 25 mIU Answer Pregnancy Test (Cup) 25 mIU Clearblue +/– 25 mIU Confirm 1-Step Pregnancy Test 25 mIU Equate Pregnancy Test 25 mIU First Response Early Result Pregnancy Test 25 mIU One Step Be Sure Pregnancy Test 25 mIU Walgreen Digital 25 mIU e.p.t. Home Pregnancy Test (one line = not pregnant; two lines = pregnant) 40 mIU e.p.t. Certainty Digital Test 40 mIU Fact Plus Pregnancy Test 40 mIU Clearblue Digital 50 mIU CVS Cartridge Pregnancy Test 50 mIU CVS Midstream Pregnancy Test 50 mIU Drug Emporium Brand Pregnancy Test 50 mIU e.p.t. +/– Test 50 mIU early Pregnancy test 50 mIU RiteAid Brand Pregnancy Test 50 mIU Target Brand Pregnancy Test 50 mIU Walmart Brand Pregnancy Test 50 mIU Walgreens Pregnancy Test 100 mIU False positives False positive results are rare in home pregnancy tests. Today, HPTs have a greater than 90 percent accuracy. However, you may have a false positive if You’re taking injections of the hormone hCG to induce ovulation or for any other reason; it takes 14 days for 10,000U of hCG (a standard dose) to completely clear your system. You recently had a miscarriage or ectopic pregnancy, and the hCG levels have not dropped to a negative range yet. (This can take up to four weeks.) You have an extremely rare form of cancer called a choriocarcinoma. Choriocarcinoma occurs in 2–7/100,000 pregnancies. The cancer is a cancer of the cells that would normally form the placenta. This cancer usually follows a full-term birth, miscarriage, or other pregnancy loss. This is a fast-growing cancer, so if you recently had a pregnancy loss of any kind and have a positive home pregnancy test and heavy bleeding, you must see a doctor immediately. False negatives The urinary test for pregnancy can show that you are not pregnant when in fact you are. These are called false negatives. The most common reason for this is that you test the urine too soon after ovulation. A second problem arises if you do not wait long enough to read the test. Finally, the urine may be too diluted. Using the first morning urine can decease the false-negative rate. The danger of a false negative is when there is an uncommon problem of an ectopic pregnancy, which is when a pregnancy implants outside the uterus — usually the fallopian tube. If you are undergoing fertility treatment, particularly IVF, you may be cautioned about using HPTs because of the false negative issue. If you use an HPT anyway (we know you might) it is best to check with your clinic before you stop any medication or start a new treatment cycle. Coauthor Lisa knows firsthand how “I got a negative” can turn into “Oh my, you’re pregnant.” She recalls one patient who had finished a Clomid/IUI cycle and reported a negative HPT and a menses. Later, when a baseline ultrasound was done to start the next treatment cycle (an IVF cycle), there was a gestational sac in the uterus! The patient had done the test too early and didn’t explain that her “menses” was only spotting. This is why many clinics require a blood test to confirm whether you are pregnant or not. The real danger with a false negative is that the person assumes one negative test means there is no chance she could be pregnant and misses the presence of an ectopic pregnancy.

Article / Updated 09-02-2021

Yay! Can you believe it? You made it out of the Infertility Club, and you are now part of the Pregnant Club. We knew you could do it! So, no worries, right? Well, maybe not so much. You may have just replaced one set of worries with another. No sweat! In this list, we offer some help as you “graduate” from your fertility clinic to your obstetrician’s office. Good pregnancy or not? So, the pregnancy test is positive — now what? The hormone that is measured for pregnancy is human chorionic gonadotropin. Specifically, it’s one of the components of the beta chain and is thus called beta hCG. For the most part, only the pregnancy — the trophectoderm, specifically — makes hCG, so any amount of hCG is a sign of an implantation of an embryo and shows in the blood roughly ten days after ovulation. As the pregnancy grows, more hCG is produced. A normal pregnancy will secrete a normal amount of hCG, which is a rise of more than 60 percent in 48 hours. Frequently, the rise is said to double every 48 hours, but that’s not always true, and a normal pregnancy may not have a doubling of the hCG every 48 hours. What does low progesterone mean if you are pregnant? The issue of low progesterone when you are pregnant is whether the low progesterone is a sign of an abnormal pregnancy or whether the low progesterone is causing an abnormal pregnancy. With very few exceptions, an abnormal pregnancy will cause low progesterone. This is especially true if the pregnancy has an abnormal number of chromosomes. Considering that this is the cause of the low progesterone, treating a low progesterone with progesterone makes little sense. That having been said, many physicians prescribe progesterone and there seems to be no adverse effects of doing so. What is a biochemical pregnancy? Somewhat aggravatingly, the term “biochemical” has crept into the lexicon of infertility. It implies that somehow a biochemical pregnancy is unique. The reality is that a biochemical pregnancy is a pregnancy that fails to grow to a size that can be seen on ultrasound or diagnosed if the pregnancy tissue is passed vaginally and assayed by pathology. Most biochemical pregnancies fail to progress because they are genetically abnormal with an abnormal number of chromosomes. What is a pregnancy of unknown location? A normal pregnancy will grow to a size where it can be seen on ultrasound somewhere in the fifth week of pregnancy (calculated from the first day of the last menstrual period). By the sixth week, a normal pregnancy will be seen on ultrasound as a gestational sac (GS) — the pregnancy unit. If the GS is in the uterus, it is termed a clinical pregnancy even if it is not normal and ends as a miscarriage. If the pregnancy is in the tubes and can be seen on ultrasound, it is called an ectopic pregnancy. Sometimes there is a pregnancy that is developing abnormally in the uterus or in the tube and cannot be seen. This is a pregnancy of unknown location and is usually treated as an ectopic pregnancy. Bleeding is bad, right? What about first trimester bleeding? Bleeding early in a pregnancy is a scary and concerning problem. Sometimes, it is the first sign that something is terribly wrong with the pregnancy and the pregnancy will end as a first trimester loss. Other times the bleeding has no significant correlation to the outcome of the pregnancy. First trimester bleeding is common. Over 25 percent of pregnant patients experience vaginal bleeding sometime before week twelve of a pregnancy. Of those women who bleed in the first trimester, a little over half miscarry. However, not all bleeding is the same. Some women will have a small amount of bleeding with no cramping while other women will experience heavy bleeding and cramping. Women who have heavy bleeding are three times more likely to miscarry. Those women with light bleeding, no cramping, and bleeding less than two days have no increased chance of miscarriage when compared to women without bleeding. If you are spotting or bleeding, contact your physician. Most probably, she will draw blood to measure the hCG and or perform an ultrasound. The thing to remember is that no amount of measuring the pregnancy by the hCG or ultrasound will alter the course of the pregnancy. At best, the information can distinguish a normal pregnancy from an abnormal pregnancy and help determine what action to take. What about exercise? Regular exercise has been associated with a number of health benefits. ACOG recommends that a pregnant woman, at a minimum, should maintain her pre-pregnancy level of exercise. So, if you are one of those fortunate people who have a healthy lifestyle, being pregnant is no excuse to stop. However, for the rest of the world, the pre-pregnant and pregnant period are a good time to develop a healthy lifestyle incorporating sound eating habits and exercise. In 2008, the U.S. Department of Health and Human Services issued guidelines for physical activity. The guidelines suggest that healthy pregnant and postpartum women should do at least 150 minutes of moderate-intensity exercise, such as brisk walking, spread over the week. If a woman has a very high prepregnant level of activity, it is okay to continue that when pregnant after a discussion with your obstetrician to make sure there are no reasons for reducing her exercise level. There are obvious pre-pregnant conditions that are absolute contraindications when pregnant, such as significant heart disease, severe lung disease, incompetent cervix, abnormal placement of placenta (previa), multiple gestations, or severe anemia. But most women are aware of these conditions and should be under the care of their OB prior to conceiving. A number of less severe conditions may suggest the need to restrict a woman’s level of aerobic exercise, but these can be discussed with the OB. Not all types of exercise carry the same risk, so the type of exercise matters. For example, walking, swimming, stationary cycling, and yoga are safe. Exercises such as contact sports, those activities with a high risk of falling, sky or scuba diving, or “Hot Yoga” should be avoided. If you are exercising and you feel anything unusual that suggests you should stop exercising (think bleeding or significant pain), then stop exercising. This is definitely not a no pain, no gain situation. Can I fly when I’m pregnant? Coauthor Dr. R recalls, “Once when I was a young, mouthy adolescent, my mother asked if she could fly somewhere and I asked if she had a broom — only once did I make that mistake.” So, can you fly when pregnant? Yes — just use an airplane. Air travel is safe when a woman is pregnant, especially in early pregnancy. Turbulence can’t be predicted, so the seatbelt should be used at all times. Most people do not fly frequently enough to be harmed by the increased cosmic radiation, but flight attendants and pilots may be. Pilots and flight attendants need to contact their employer for further information and company policy regarding flying when pregnant. Should I quit my job? According to the ACOG practice bulletin, working during pregnancy is generally safe. As of 2015, 70 percent of women with children under the age of 18 were in the labor force. Of these, 56 percent of pregnant women worked full time during the pregnancy. Jobs where it may not be safe to work while pregnant require individual investigation. For example, what about jobs where there are toxic chemicals? While thousands of chemicals are used in industry today, very few have been documented to be harmful to a pregnant woman. However, some chemicals are considered to increase risks for fetal anomalies and miscarriage. These include heavy metals like lead, mercury, or arsenic; some pesticides and herbicides; some solvents; ionizing radiation; and chemotherapeutic medicines. OSHA regulates exposure to some of these potential hazards, but if you are concerned about the risk, you can consult the chemical’s data safety sheet, CDC-NIOSH, and your employer. Sometimes, accommodations can be made to make sure you are comfortable with any potential risk. The information available on night shift work or extensive occupational lifting is mixed, but there may be a slight increased risk for miscarriage. Studies did show a slight increase in the risk for preterm birth for some work conditions, such as work where the person was standing for more than three hours or carrying more than 11 pounds. Physically demanding work has been shown to increase low back pain and musculoskeletal problems. For these conditions, accommodations have been shown to reduce the risk. For example, where the work involves standing for prolonged periods of time, things like floor mats, sit-stand workstations, support hose, and appropriate shoes have been shown to help. Jobs requiring lifting do pose a risk of back pain and musculoskeletal injuries. The National Institute of Occupational Safety and Health has made recommendations for pregnant women for weight limits. An excellent summary of these recommendations is published by ACOG. Should I get a flu shot? The answer to this is easy: Yes! Unfortunately, vaccination has become a hot topic with fears of risks like autism from being vaccinated. These undue fears have already needlessly cost lives. In recent years, there have been 24,000 deaths in the United States per year due to influenza. In the 2009 influenza pandemic (an infection that is prevalent over an entire nation or worldwide), pregnant women between the ages of 18 and 29 accounted for 16 percent of deaths from the influenza infection. A study done by the FDA’s Vaccine Adverse Event Reporting System reported no or mild adverse outcomes in over 2 million people vaccinated. There were no adverse effects on the infants. This is one example of how bad science, fake news, and conspiracy theories have caused needless deaths. When should I see my ob/gyn? You have a positive pregnancy test. Yay! Then another one. Double-yay! But you are still at the fertility clinic. There will come a time when you need to move from the care of your REI to the care of an obstetrician (OB). There is no set standard. Some REIs like to monitor patients and manage their early obstetric care. Other REIs do a single ultrasound to document that the pregnancy is in the uterus and that the fetus has fetal heart motion. When your REI tells you it’s time to move on, as coauthor Lisa likes to say, “You have now graduated!” It is a very good idea to have chosen an obstetrician, the physician who will manage your pregnancy and deliver your baby, prior to treatment for infertility so that when the good news comes, the OB is already on the team. Occasionally, there may be a question or problem that is more appropriately handled by your OB rather than by the REI. So, having an established relationship with an OB will avoid the problem of whose patient you are. Also, OBs differ in how they handle certain problems, and since that is the person who will manage you to the finish line, it is helpful to already have that doctor on board. Do I have to stay on my medication? Sometimes women feel that they are not pregnant and will stop their medications. Whether this can cause a pregnancy to fail is up for debate, but a good rule of thumb is to stay on your medications until your REI has told you exactly what to do with your meds. Also, this is probably not the best time to start meds that you were not on unless you clear this with your REI. On the other end of the spectrum, if the pregnancy test was positive, you may figure you are pregnant so, what the heck, you can stop all those injections and other meds from the fertility office. No! There was a reason that the fertility clinic prescribed the medications, and you are most often sent on to see your OB with a list of instructions on what meds to stay on and when to stop. Even though you are an IVF “glad grad,” you still need the drugs. So, don’t change anything until you talk to your OB. Dealing with a UTI Urinary tract infections (UTIs) are the second most common problem for pregnant women behind anemia. Left unattended to, they can cause severe infections of the kidneys (pyelonephritis), which can be harmful to the pregnancy. So, do you start by downing a gallon of cranberry juice and hope that cures the problem, or is it time to consult your physician? The most common treatment for UTIs is oral antibiotics, which. properly prescribed and taken, are safe in early pregnancy. When in doubt, consult your physician. What is happening to my skin? Skin changes are common in pregnancy. Common changes include dark spots on the breasts, nipples, or inner thighs and sometimes brown patches on the face (melasma). Other changes include linea nigra (a dark line running from the belly button to the pubic hair line, stretch marks, acne, varicose veins, and changes in hair and nail growth. Some of these changes are due to the hormones that are present during pregnancy, and some, such as varicose veins, are due to the physical presence of the fetus as it gets bigger. Over-the-counter medications that can be used during pregnancy include topical benzoyl peroxide, azelaic acid, and glycolic acid. Some prescription medications should not be used during pregnancy, and these include isotretinoin, oral tetracyclines, and topical retinoids. Many women experience increased hair growth, perhaps in places where there had been very little hair. These changes usually return to normal by six months postpartum (after the child’s birth), but many women experience hair loss in the first three months postpartum. Varicose veins are common in pregnancy due to the weight of the pregnancy as it grows and places pressure upon the veins that return the blood from the legs. Varicose veins are almost impossible to prevent, but certain physical accommodations can be made to lessen swelling and discomfort. These include not sitting with your legs crossed, moving around, elevating your legs as often as you can, considering support hose (consult your OB first), and avoiding (good luck) constipation by eating high-fiber foods and adequate liquids.

Article / Updated 09-02-2021

If we have eggs, we need sperm to create embryos! So, while you were having your eggs retrieved for insemination, your partner was probably collecting a sperm sample. Or, perhaps you are using frozen sperm from your partner or a sperm donor. Regardless of the method or source, the laboratory will be working with that specimen to get it ready to meet its partner. First comes identifying the appropriate specimen, and then the team takes it through a series of “washings” in special media to remove all the seminal fluid and isolate the sperm (pretty much like it’s done for an intrauterine insemination). As the eggs are prepped, the sperm specimen is kept in an incubator until it’s time to either inseminate the eggs by conventional methods or by going a little bit more high tech. Conventional sperm insemination If your partner’s sperm is normal and your eggs are going to be fertilized in the lab with normal insemination, the next steps are as follows: The sperm are washed, and the egg is separated from the follicular fluid. It still has its cumulus, which helps to activate the sperm. For standard IVF, your eggs (up to six to eight per dish) and sperm are placed a in dish that has wells so that each egg, or at most a couple, have its own chamber. This step used to take place in a petri dish, a flat-bottomed round glass or plastic dish, which was labeled with your name, lab number, the date, and the number of eggs in the dish. This is so passé today. The dish is placed in an incubator so the eggs and sperm can be kept at body temperature. They’re kept in a nutrient solution (culture medium), which provides conditions as similar as possible to those in the body. Different labs use different culture media, and this is one way that labs differ from one another. However, today most labs purchase their media from a limited number of companies and there are only a few different types of media, so the media is standardized across the industry. Conventionally inseminated eggs are left alone for 16 to 20 hours. The day after the retrieval, embryology takes the dish out of the incubator, strips off the cumulus (which has by now been greatly loosened by the action of the sperm), and checks the eggs. What they hope to find is two pronuclear (2PN) embryos, or embryos that have two visible circles lined up next to each other. These embryos contain the genetic material from each parent. High-tech sperm injection Since the advent of intracytoplasmic sperm injection (ICSI) the use of conventional insemination has decreased significantly. A report by the CDC states that from 1996 to 2012, the use of ICSI for male factor infertility rose from 76 percent to 93 percent and for couples without male factor from 15 percent to 66 percent. Using ICSI for male factor increases the chance that the egg will fertilize. Some men with male factor have sperm that can’t penetrate the shell of the egg, and ICSI bypasses this problem. So, the use of ICSI for male factor makes sense. For couples with no male factor there is less of a need to do ICSI. The problem is that there is no test that accurately identifies the man with a normal semen analysis where his sperm can’t fertilize the egg. The couple undergoes the entre IVF process, places the sperm and eggs together, and the next day finds that none of the eggs fertilized. This is not common but extremely disappointing when it occurs. For that reason, many IVF programs have significantly increased the use of ICSI. If you’re planning to freeze some or all of your embryos for use at another time, your clinic may freeze them at the 2PN stage. Some centers grow all your embryos out to blastocyst stage and freeze only those that make it to blastocyst.

Article / Updated 09-02-2021

Infertility and getting pregnant is no exception to the world of “fake news.” Is it real or isn’t it? Surprisingly enough, this phenomenon has existed in the field of science and medicine for . . . ever. From the early “snake oil salesmen” to the pills and potions of self-proclaimed shamans to the latest news bulletin claiming that immortality is just around the corner, medical professionals often find themselves trying to separate the glitter from the goods. How many of the following tidbits have you heard — or believed? News for rodents While technically not in the “fake news” category, a new (pick one) drug, procedure, treatment has been found to reverse anything when tested in mice. As a news producer once told co-author Jackie, “Great news for rodents!” It’s crucial to remember that testing in animals, while an important step in determining the effectiveness and safety of a medical treatment, is only the first step. Most of these do not make it past the first step — and remain a good option only for rodents. The scientific chain of proof before a treatment can be considered for use in humans (or even more complex mammals!) is a long one. Those in the medical community generally reserve judgment on these tidbits, which may very well stop at being rodent food for thought! Reading about medical miracles Everyone wants to jump on the bandwagon when it comes to reporting stories of medical miracles. Keep in mind that most (or make that all) medical journals avoid the use of the word “miracle” at all costs! Medicine and science are long and painstaking processes and rarely come across a “gimme” (or a simple, great cure) that appears out of nowhere, also known as a miracle. Actually, ASRM cautions infertility specialists against ever using the world miracle, as it is a setup for disappointment and doesn’t meet the burden of proof required. But, miraculous stories of women giving birth at (pick one) 50, 60, 70, or 80 without (considerable) assistance is the kind of story that sells. Whether a celebrity-based magazine about people (we’re not naming any names here!) or an outright tabloid, consider the source. Celebrity fecundity (also known as fertility) Hollywood would like us to believe that celebrities are aging without any of the ill side effects that we humans encounter including weight gain, wrinkles, and loss of fertility. Photoshop or CGI (computer-generated imagery) goes a long way in helping to sustain this myth. So, does leaving out just a “little bit” of crucial information. For example, the 55-year-old female celebrity who has “miraculously” (there’s that word again!) given birth to her first child with just a glass of wine and a prayer was more likely utilizing the best that ART has to offer, including donor eggs or egg freezing. Really, how else can celebrities maintain the pedestal that we often put them on without appearing to be better than the rest of us at defying all odds? They can’t. Cell phones decrease male fertility A literature search on PubMed for cell phones and male infertility turned up almost 50 articles, with some articles showing a difference and some not showing a difference. Many of the articles focused on the semen analysis but not the actual chance of achieving a pregnancy. Since the amount of time a man uses his cell phone varies considerably, there are a number of other things that may influence the semen analysis. For example, is the student, coffee-house devotee using his phone the same as the 95th-floor, high-powered executive? A representative study published in 2015 found no difference in semen results based upon cell phone usage. There was a reduced sperm count based upon internet usage with those using the internet more frequently having lower sperm counts. That raises the contentious issue of whether sitting and thus increasing testicular temperature can reduce the sperm counts. A 2018 study looked at cell phone usage with 4G for rats. Who knew rats had cell phones? These poor little fellows were exposed to varying lengths of exposure to 4G LTE cell phones and — if that weren’t enough, egad — their testicles were assessed for number of sperm cells. The longer the exposure, the lower the number of sperm cells. Not the best study to volunteer for if you are a male rat. But wait: Cell phones aren’t the only source of non-ionizing radiations. What about laptops, Wi-Fi, microwave ovens, and on and on. After an extensive review of the currently available research, the authors of a 2018 review concluded that non-ionizing radiation may decrease sperm parameters. They could not conclusively say this was so nor did they say the evidence conclusively demonstrated that cell phone usage causes infertility. So again — maybe! Increased longevity means a larger fertility window Not so much. The increased longevity (humans living longer) arises from things like antibiotics, anesthesia, pharmaceuticals, immunization, and sanitary conditions, to mention a few. The effect of these advances in the 19th and especially the 20th century increased the worldwide life expectancy of women from 54 years in1900 to 75 years in 2019. (U.S. rates are even higher at 81 years!) The average life expectancy in 1800 was between 30 and 40. So the increase in life expectancy derived from something that could be corrected. For example, women becoming infected after childbirth died at an alarming rate until antibiotics were developed that cured the infection. In 1900, for every 1,000 births, seven women died and 40 percent were due to infections. By 1997, the maternal mortality decreased to less than 0.1 per 1,000 deliveries. But nothing has changed the underlying problem with age-related infertility. No medication has been developed that allows women to make eggs after she is born. No medication nor intervention has been devised that prevents the ovary from destroying the pool of eggs. So, while life expectancy has increased because of problems that have solutions, living longer has not translated into longer fertility potential because nothing fixes the issue of limited egg number and rapid egg usage and wastage. Men don’t undergo menopause Hah! The first thing to understand is that male menopause is not the same as male fertility. The debate about age and male infertility rages, but in general, males can father children well into their 70s and maybe even 80s if they are capable of ejaculating. But males experience a decline in their testosterone levels as they age. Colloquially, this is called “low T.” The symptoms include fatigue, depression, sexual dysfunction, weakness, and loss of muscle mass, just to name a few of the symptoms. Not all doctors agree that low T, as male menopause, actually exists, but if you ask men, they will tell you that it does. Measuring the testosterone levels may define a cause of male menopause. For men symptomatic with low T, testosterone replacement may be a solution. Looking good means your fertility is good Just because you can pass for 30 something, be aware that your ovaries have a mind of their own! So, you look great, feel well, eat healthy, and exercise often — congratulations! These are all excellent lifestyle choices that can help you maintain good health, to some degree, in the short and long term. They can certainly give you a great base for gestating a child and raising one with healthy habits. But, if you are 40 something, your ovaries are not in on the secret. Your ovaries will always reflect your biologic age no matter how good you look and feel. You can glue your embryos to your uterus While this may appear to be the peak of fake news, hold on, maybe you can, sometimes. Have we confused you yet? In 2012 a study was published that found no increased pregnancy rate when embryo glue was used. A Cochrane database report in 2014 said it might improve pregnancy rate. So, where do we stand? First of all, is embryo glue actually glue? Is it like that white pasty glue we (well, apparently not coauthor Lisa) ate when we were in the third and fourth grade? Mmmmm, delicious! No! Embryo glue is not glue at all. Embryo glue is a solution that contains hyaluronic acid. Hyaluronic acid is a naturally occurring substance in the secretions in the female reproductive tract. It tends to make things sticky. So dipping an embryo into the solution may make the embryo sticky and thus help with implantation. A study published in 2018 used a solution of hyaluronic acid–enhanced media for frozen embryo transfers. They found that for the first transfer, the pregnancy rate was less than when not using the solution. When the patient had a second frozen embryo transfer and the solution was used, there was no difference seen. If the patient returned for a third frozen embryo transfer, then the use of the solution did improve the pregnancy rate. If a person has had two normal appearing embryos transferred and has no evidence that they implanted, she may have recurrent implantation failure (RIF). Some physicians have suggested that for this group of patients (those with RIF), the embryo glue may help. Procreation vacations work Vacations are great, but do they increase the chance for a pregnancy? Sorry guys, not so much. Before you book a multi-thousand-dollar vacation hoping it will help you get pregnant, you may want to reflect on what is keeping you from getting pregnant in the first place. Males with very low counts, women with blocked tubes, women who don’t ovulate on their own, women with endometriosis, age-related infertility — these and other diagnostic categories for infertility will not be helped by going on a vacation. It’s hard to imagine how lying in the sun in Tahiti can magically unblock tubes. So why even make the suggestion? But, does this work for those patients with unexplained infertility? The reasoning is that coping with infertility increases stress. Vacations are supposed to reduce stress, ergo, taking a vacation will help you get pregnant. There are heated debates about the importance of stress in causing infertility. There is little debate as to whether infertility causes stress. And if you don’t know the answer to this debate, you haven’t really had infertility. Infertility causes stress! Under normal circumstances, taking a vacation can reduce stress. However, taking a vacation to improve the chance of pregnancy may actually increase the stress level — there is no credible evidence looking at this possibility. Taking a vacation to get a vacation from fertility treatments makes more sense. Breaking the daily grind of fertility treatment can be much needed and the expense is more than worth it. Adopt and you’ll get pregnant Maybe, but the adoption does not increase the normal treatment independent pregnancy rate (the rate of pregnancy without treatment). There is a chance that any person who has stopped fertility treatments and does nothing will get pregnant without any further treatment. If you evaluate a large number of patients who have adopted, some of them achieved a pregnancy on their own. But the chance is the same as for those who did not adopt. An interesting study from 2018 looked at what happened five years after patients had undergone IVF. The majority did no more IVF. For those who had adopted, almost 7–8 percent had a spontaneous pregnancy. Overall, five years after IVF over 90 percent of the patients were living with children in the family. Some were from more IVF, some from spontaneous pregnancies, some as stepparents, and some from adoption. For this study almost 10 percent had a spontaneous pregnancy after stopping IVF and having not been successful with the IVF they had done. Various studies will have somewhat different figures, but the overall point is that most people can have children in their family — just not as easily as they had expected.

Article / Updated 09-02-2021

Are there long-term health effects of fertility medications, or gonadotropins, which are natural hormones normally produced by the body? When you go through menopause, the blood levels of all of these hormones are going to be far higher than anything that can be attained by injecting fertility medication. However, when given to women of reproductive age, whose ovaries can and do respond, they are powerful stuff. Anyone who takes them through even one cycle can attest to the physical and emotional effects of having one’s hormones surging at a much higher level than nature ever intended. Do people suffer long-term effects 2 or 20 years down the road? No one knows for sure, but here are the most recent conclusions on the safety of taking gonadotropins. Effects on the mother At this time, experts have no solid proof that taking gonadotropins has any long-term effect on women. Some studies have shown a possible link between fertility medications and ovarian cancer, but other studies have not supported these findings. The actual risk to the mother is short-term hyperstimulation, which occurs in about 1.5 percent of IVF cycles and occurs so severely that the mother needs to be admitted to a hospital 0.34 percent of IVF stimulation cycles. Infection, significant bleeding, and anesthetic complications occurred in less than 0.1 percent of the cycles. From 2000 to 2011, there were no maternal deaths due to IVF. One thing most studies have agreed upon is that the risk of ovarian cancer is higher in all women who’ve never become pregnant, regardless of whether or not they’ve taken fertility medications. So, if you’ve taken fertility drugs for any amount of time and never had a child, make sure to consult your gynecologist. Like many things, the recommendations about frequency of visits and what testing to do changes constantly as more is learned about heritability of disease. Your healthcare can be tailored to meet your set of circumstances, and thus global recommendations may not be appropriate for you. Only a close working relationship with your healthcare provider can make sure you have the optimal healthcare. Effects on the baby No one is sure whether ART procedures will have a long-term effect on the children conceived through their use — the children born through high-tech methods such as in vitro fertilization (IVF) aren’t old enough yet. The oldest IVF baby, Louise Brown, was born in 1978. So, is there something that will show up when the IVF conceived children reach 60, or 80, or 100? Techniques such as ICSI (intracytoplasmic sperm injection) and assisted hatching are even newer; they’ve only been used extensively since the 1990s. Because research is ongoing even as children are being born, high-tech treatment has an element of risk simply because the jury’s still out on long-term effects. Given the limitation data, what do we know about those people who have been conceived through IVF? Trying to accurately determine if IVF is harmful to the children it creates is difficult. One complication is trying to understand whether any harm is due to the diagnosis of infertility itself or is related to the procedure of IVF. Most authors of the studies evaluating the effect of IVF suggest that some of the risk is due to the diagnosis of infertility. Some studies have suggested that high-tech babies have lower birth weight (33 grams [1.16 ounces] lighter) and earlier delivery (by half a day). A 2016 study concluded that many obstetric and neonatal risks were elevated in singleton IVF pregnancies, including such things as birth defects and neonatal death. While the increased risks were real, the actual chance of one of these risks is low because these complications occur infrequently (8.3 percent prevalence in IVF babies as opposed to 5.8 percent prevalence in spontaneously conceived babies). More twins and triplets are born to moms using fertility meds, and multiples more commonly have low birth weight and developmental delays. Also, more babies are born to older mothers through high-tech treatment, and older women tend to have more complicated pregnancies than women under age 35. It‘s important to note that up to this point, no effect of fertility medications themselves on the babies has been shown. Furthermore, fertility medications are natural hormones, normally present in the body. And even though they may be present at higher than normal values during the stimulation phase, they’re all well out of your system by the time the embryo implants. So whatever effect these medications may have would have to be on the egg, and these effects are purely hypothetical. Still, only time will tell for sure.