Our team here at the Center for Human Reproduction has recently developed an infographic explaining one of the most common causes of female infertility: unexplained infertility. This diagnosis is given to 30% of infertility cases and yet, we believe it really is a non-diagnosis. In our clinical experience, with proper testing, up to 90% of unexplained infertility diagnoses can be attributed to treatable causes.

IUI: An IUI can be done with no medications or a number of different medications to help develop and ovulate one or two eggs. Around day 14 of a woman’s cycle, the insemination takes place which deposits sperm inside the uterus. This greatly increases the number of sperm at the junction of the uterus and fallopian tubes, the distance they have to swim to meet the egg, and thus increases the chances of natural conception for many people.
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The take home message of these studies is that when gonadotropins are given to this patient population at a dose that doesn’t put the patient at significant risk of twins (like the 75 units in the Huang study), they are no better than oral medications (clomid and letrozole) at producing successful pregnancies. This is important because clomid and letrozole are also cheaper to purchase (hundreds vs. thousands of dollars) and easier to administer (oral rather than injectable). For this reason, many clinics have moved away from using gonadotropins in IUI cycles.
After the retrieval procedure, you'll be kept for a few hours to make sure all is well. Light spotting is common, as well as lower abdominal cramping, but most feel better in a day or so after the procedure. You'll also be told to watch for signs of ovarian hyperstimulation syndrome, a side effect from fertility drug use during IVF treatment in 10% of patients.
Treating secondary infertility, like primary infertility, will depend largely on any underlying medical conditions. Through the Couples Clinic at UW Health's Generations Fertility Care, both members of the couple undergo a routine evaluation. Since infertility is not simply a woman's problem, evaluating both members ensures the most effective treatments can be recommended.  
Embryos are transferred to the uterus. Embryos that have developed from the fertilization process will be placed in the uterus, normally 3 to 5 days after retrieval, so that they can embed. If this process is successful, pregnancy will occur and IVF is considered a success. If it’s not, you may use a frozen embryo that you have saved from a previous round of IVF to try again.
In cases where the man's sperm count is extremely low or there is poor motility (movement of the sperm), doctors may combine IVF with a procedure called intracytoplasmic sperm injection. In this procedure, a sperm is taken from semen -- or in some cases right from the testicles -- and inserted directly into the egg. Once a viable embryo is produced, it is transferred to the uterus using the usual IVF procedure.

Federal regulations in the United States include screening requirements and restrictions on donations, but generally do not affect sexually intimate partners.[185] However, doctors may be required to provide treatments due to nondiscrimination laws, as for example in California.[114] The US state of Tennessee proposed a bill in 2009 that would have defined donor IVF as adoption.[186] During the same session another bill proposed barring adoption from any unmarried and cohabitating couple, and activist groups stated that passing the first bill would effectively stop unmarried people from using IVF.[187][188] Neither of these bills passed.[189]

Take a look at your lifestyle. Have any of your habits changed since you conceived baby number one? For instance, is your diet still on track, or is there room for improvement? Getting your eating plan up to baby-making speed may help you close in faster on conception. Has your caffeine consumption gone up now that you’re a mom? That’s understandable, but too much caffeine isn’t great for fertility. Has your smoking habit returned? If yes, it’s time to kick butt, since smoking ages your eggs and decreases fertility. Are you getting way too little sleep? That may be likely, especially if your first child is keeping you up at night, but skimping on sleep can mess with your hormones — and possibly your fertility. If any new unhealthy habit has slipped into your lifestyle, now’s a great time to put the brakes on it. And it’s not just about your habits. Is your partner kicking back one too many beers each night? That could be affecting his sperm quality. Ditto for smoking or an unhealthy diet. If your partner’s lifestyle needs a little fine-tuning, make efforts to get his back on track, too.
The Latin term in vitro, meaning "in glass", is used because early biological experiments involving cultivation of tissues outside the living organism were carried out in glass containers, such as beakers, test tubes, or Petri dishes. Today, the scientific term "in vitro" is used to refer to any biological procedure that is performed outside the organism in which it would normally have occurred, to distinguish it from an in vivo procedure (such as in vivo fertilisation), where the tissue remains inside the living organism in which it is normally found.
Coping with secondary fertility can be tough. Endless doctor appointments, tests, procedures, and medications. Sleepless nights. Time and energy away from your little one. Guilt over wanting another pregnancy when many women are struggling to have just that. Stress between you and your partner. Sadness when you get invited to yet another baby shower — and guilt for even feeling that way.
According to the data collected for 2014, these are the IVF success rates nationally, when using non-donor eggs, per egg retrieval. (These are not per cycle. In other words, these are the odds of a live birth after one egg retrieval, which may mean conception with fresh eggs/embryos in the cycle of the egg retrieval ​or after a frozen embryo transfer cycle in the following months.) 

The common thing that happens once learning about the unexplained infertility diagnosis is shifting blame or incurring guilt. You may feel a sense of individual responsibility for the news, and be concerned about the effects that this will have on your relationship and your current partner. Perhaps you feel like you waited too long to start a family or have anxiety finding the right parenting partner that you associate now with your infertility. Remember, it’s no one’s fault.
It’s not because you just ate a whole lot of greasy food (myth!). Sudden, out-of-control acne could be blamed on fluctuating hormones (from your period or menopause), a whole lot of stress, or a medication side effect. It may also be a sign of polycystic ovarian syndrome. That’s because in women with PCOS, ovaries make more androgen—the “male hormone”—than normal. Elevated levels may lead to adult acne flare-ups, as well as excessive facial or body hair, and even male-patterned baldness. These natural acne remedies may help your skin.
Bloating: Fertility medications can heavily impact how your body retains water, leading to the dreaded side effect of bloating. This is especially common in your midsection, where fluid can build up near the ovaries (creating abdominal tenderness, too). You can combat bloating by increasing your fluid intake and participating in light exercise such as walking.
Problems with the uterus: There are many conditions related to the uterus that can cause secondary infertility. Scarring can occur during a dilation and curettage (D&C) or Cesarean delivery that can create adhesions inside the uterus that interfere with future pregnancies Fibroids or polyps are benign (non-cancer) growths inside the uterus that can impair pregnancy. A retained placenta can cause infection and uterine scarring.
Infertility may have psychological effects. Partners may become more anxious to conceive, increasing sexual dysfunction.[17] Marital discord often develops, especially when they are under pressure to make medical decisions. Women trying to conceive often have depression rates similar to women who have heart disease or cancer.[18] Emotional stress and marital difficulties are greater in couples where the infertility lies with the man.[19]
After your body releases an egg, the hormone progesterone kicks in to build and maintain the lining of the uterus. It makes your body temperature go up slightly. So taking your temperature with a basal thermometer every morning before you get out of bed can help you figure out if you ovulated. You can buy these thermometers at the drugstore. They're inexpensive, but they aren't as accurate as other ways of tracking ovulation.
Availability of IVF in England is determined by Clinical commissioning groups. The National Institute for Health and Care Excellence recommends up to 3 cycles of treatment for women under 40 years old with minimal success conceiving after 2 years of unprotected sex. Cycles will not be continued for women who are older than 40 years old.[156] CCGs in Essex, Bedfordshire and Somerset have reduced funding to one cycle, or none, and it is expected that reductions will become more widespread. Funding may be available in "exceptional circumstances" – for example if a male partner has a transmittable infection or one partner is affected by cancer treatment. According to the campaign group Fertility Fairness at the end of 2014 every CCG in England was funding at least one cycle of IVF".[157] Prices paid by the NHS in England varied between under £3,000 to more than £6,000 in 2014/5.[158] In February 2013, the cost of implementing the NICE guidelines for IVF along with other treatments for infertility was projected to be £236,000 per year per 100,000 members of the population.[159]
A woman's age is a major factor in the success of IVF for any couple. For instance, a woman who is under age 35 and undergoes IVF has a 39.6% chance of having a baby, while a woman over age 40 has an 11.5% chance. However, the CDC recently found that the success rate is increasing in every age group as the techniques are refined and doctors become more experienced.
IVF using no drugs for ovarian hyperstimulation was the method for the conception of Louise Brown. This method can be successfully used when women want to avoid taking ovarian stimulating drugs with its associated side-effects. HFEA has estimated the live birth rate to be approximately 1.3% per IVF cycle using no hyperstimulation drugs for women aged between 40–42.[63]
DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage,[31] smoking,[28] other xenobiotic DNA damaging agents (such as drugs or chemotherapy)[32] or other DNA damaging agents including reactive oxygen species, fever or high testicular temperature.[33] The damaged DNA related to infertility manifests itself by the increased susceptibility to denaturation inducible by heat or acid [34] or by the presence of double-strand breaks that can be detected by the TUNEL assay.[35]
Once the medications take their effect, your doctor will use a transvaginal ultrasound to guide a needle through the back wall of your vagina, up to your ovaries. She will then use the needle to aspirate the follicle, or gently suck the fluid and oocyte from the follicle into the needle. There is one oocyte per follicle. These oocytes will be transferred to the embryology lab for fertilization.
Dr. Gorka Barrenetxea provides us with a practical case of secondary infertility that occurs more commonly than one may think. A couple, throughout their lifetime, can have children with 20, 25, 30 and 35 years, but when they decide to have a second or third child, they may encounter trouble conceiving due to the passage of time itself, Dr. Barrenetxea states.
Ovarian hyperstimulation is the stimulation to induce development of multiple follicles of the ovaries. It should start with response prediction by e.g. age, antral follicle count and level of anti-Müllerian hormone.[60] The resulting prediction of e.g. poor or hyper-response to ovarian hyperstimulation determines the protocol and dosage for ovarian hyperstimulation.[60]

If IVF were to involve the fertilisation of only a single egg, or at least only the number that will be implanted, then this would not be an issue. However, this has the chance of increasing costs dramatically as only a few eggs can be attempted at a time. As a result, the couple must decide what to do with these extra embryos. Depending on their view of the embryo's humanity or the chance the couple will want to try to have another child, the couple has multiple options for dealing with these extra embryos. Couples can choose to keep them frozen, donate them to other infertile couples, thaw them, or donate them to medical research.[90] Keeping them frozen costs money, donating them does not ensure they will survive, thawing them renders them immediately unviable, and medical research results in their termination. In the realm of medical research, the couple is not necessarily told what the embryos will be used for, and as a result, some can be used in stem cell research, a field perceived to have ethical issues.
Problems in the quantity or quality of eggs: Women are born with a limited supply of eggs and are unable to create new eggs after birth. As women approach their 40s and beyond, the numbers of eggs left in their ovaries decrease, and the remaining eggs have a higher chance of having chromosomal problems. For women where age isn’t a concern, there are other reasons that they might have a low number of good quality eggs, including autoimmune or genetic conditions and prior surgery or radiation.

Next, we’ll look at data that compares PCOS patients who took clomid alone or clomid accompanied by IUI (no studies use letrozole, so we are forced to use a study with clomid). Clomid alone produced a 17% live birth rate after 3 cycles, while clomid plus IUI produced a 19% live birth rate. Investigators concluded there was no statistically significant difference.

Costs of IVF can be broken down into direct and indirect costs. Direct costs include the medical treatments themselves, including doctor consultations, medications, ultrasound scanning, laboratory tests, the actual IVF procedure, and any associated hospital charges and administrative costs. Indirect costs includes the cost of addressing any complications with treatments, patients' travel costs and lost hours of productivity.[142] These costs can be exaggerated by the increasing age of the woman undergoing IVF treatment (particularly those over the age of 40), and the increase costs associated with multiple births. For instance, a pregnancy with twins can cost up to three times that of a singleton pregnancy.[143]


The stress of secondary infertility on an individual's life and relationships can be significant. It can be hard to find support from family and friends, especially when a woman or couple already has/have children. Sentiments such as, "you should be grateful for what you have," or, "just keep trying," almost never serve as useful advice or support. Couples and single parents can even experience resentment from other couples with infertility who are unable to even have their first child.
Any embryos that you do not use in your first IVF attempt can be frozen for later use. This will save you money if you undergo IVF a second or third time. If you do not want your leftover embryos, you may donate them to another infertile couple, or you and your partner can ask the clinic to destroy the embryos. Both you and your partner must agree before the clinic will destroy or donate your embryos.
The stress of secondary infertility on an individual's life and relationships can be significant. It can be hard to find support from family and friends, especially when a woman or couple already has/have children. Sentiments such as, "you should be grateful for what you have," or, "just keep trying," almost never serve as useful advice or support. Couples and single parents can even experience resentment from other couples with infertility who are unable to even have their first child.
While many cases of infertility remain unexplained, there may be answers in the epigenome. Unlike one’s genetic code, the epigenome is dynamic and can be modified by environmental factors and lifestyle choices. Fertility in many cases is a state which changes throughout one’s life. Given the lack of clear genetic or physiological causes of unexplained infertility, the epigenome is thought to be altered in this subset of patients. As a result, looking into the epigenetic basis of infertility can help clinicians inform treatment.
With each year that passes, your chances of conceiving decrease significantly, says Julie Tan, M.D., a gynecologist at the Cleveland Clinic Center for Reproductive Medicine, in Ohio. Sometimes even doctors downplay infertility, she notes. Most experts recommend seeing your doc after a year of unsuccessful unprotected sex if you're under age 35 and after six months if you're over 35. But if you're worried sooner, speak up. "If it's been three months and you're concerned, it's not too early to get evaluated, even though it may be premature to treat," explains Dr. Grifo. "Waiting a year to find out there's an issue with sperm count or egg supply can lead to a lot of heartache." You can start with your primary-care doc or ob-gyn but if you're not pregnant after a few months or feel your doctor isn't taking the situation seriously, see a fertility specialist.
A review in 2013 came to the result that infants resulting from IVF (with or without ICSI) have a relative risk of birth defects of 1.32 (95% confidence interval 1.24–1.42) compared to naturally conceived infants.[48] In 2008, an analysis of the data of the National Birth Defects Study in the US found that certain birth defects were significantly more common in infants conceived through IVF, notably septal heart defects, cleft lip with or without cleft palate, esophageal atresia, and anorectal atresia; the mechanism of causality is unclear.[49] However, in a population-wide cohort study of 308,974 births (with 6,163 using assisted reproductive technology and following children from birth to age five) researchers found: "The increased risk of birth defects associated with IVF was no longer significant after adjustment for parental factors." [50] Parental factors included known independent risks for birth defects such as maternal age, smoking status, etc. Multivariate correction did not remove the significance of the association of birth defects and ICSI (corrected odds ratio 1.57), although the authors speculate that underlying male infertility factors (which would be associated with the use of ICSI) may contribute to this observation and were not able to correct for these confounders. The authors also found that a history of infertility elevated risk itself in the absence of any treatment (odds ratio 1.29), consistent with a Danish national registry study [51] and "implicates patient factors in this increased risk." The authors of the Danish national registry study speculate: "our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly due to the underlying infertility or its determinants."
I conceived my first child, a son, with no trouble at all. When he was two, we thought we might have another. A year or so later, when nothing had happened, we saw a fertility specialist, who gave us every test there was. We passed each one, as the consultant put it, "with flying colours". Which left us relieved but also confounded. All I had was a new adjective to add to my diagnosis: Unexplained Secondary Infertility.
We also care about not only your physical well being, but also your emotional health. In fact, these issues as important enough to us that one of our core team members is a psychologist. Julianne Zweifel is an expert in addressing the mental aspects of secondary (and primary) infertility and she can promote emotional well being in a way that few others have the training or experience to do. If you should feel you do not wish to talk a specialist, but are struggling emotionally, please at least let other team members know-the more we hear from you, the easier it is for us to help.  
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