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."

The severity or complexity of infertility for you and your partner as a whole is also critical. Generally, patients are characterized as “subfertile” if there is only one infertility factor such as mild endometriosis, which can be improved through surgeries like laparoscopy. However, if both partners contribute infertility factors or one partner has multiple infertility factors, the chance of IVF success is significantly decreased.
Other health related problems could also cause poor egg health, low ovarian reserve, or abnormal immunological responses, which can affect conception. Stress could also play a role. We all know that menstrual cycles can be altered during times of extreme duress- and this can be emotional, physical, or environmental stressors. In these instances, the first steps should be to avoid life stressors, maintain a healthy weight, routinely exercise, avoid smoking, and reduce alcohol intake, all of which may be contributing to unexplained infertility issues. 

All pregnancies can be risky, but there are greater risk for women who are older and are over the age of 40. The older the women the riskier the pregnancy. As women get older, they are more likely to suffer from conditions such as gestational diabetes and pre-eclampsia. If older women do conceive over the age of 40, their offspring may be of lower birth weight, and more likely to requires intensive care. Because of this, the increased risk is a sufficient cause for concern. The high incidence of caesarean in older mothers is commonly regarded as a risk.
Intrauterine insemination is the process whereby a clinician will place a concentrated specimen of sperm in your uterus. For this procedure, he or she will insert a speculum into your vagina in order to better visualize your cervix. He or she will then pass a soft, thin catheter through the cervix opening and into the uterus. The clinician will introduce the washed sperm into the uterus through this catheter. The procedure is done in our office and takes 1 to 2 minutes. It is not painful and does not require anesthesia. You can return to normal daily activities immediately after an IUI.
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]

Other health related problems could also cause poor egg health, low ovarian reserve, or abnormal immunological responses, which can affect conception. Stress could also play a role. We all know that menstrual cycles can be altered during times of extreme duress- and this can be emotional, physical, or environmental stressors. In these instances, the first steps should be to avoid life stressors, maintain a healthy weight, routinely exercise, avoid smoking, and reduce alcohol intake, all of which may be contributing to unexplained infertility issues.

The main durations of embryo culture are until cleavage stage (day two to four after co-incubation) or the blastocyst stage (day five or six after co-incubation).[71] Embryo culture until the blastocyst stage confers a significant increase in live birth rate per embryo transfer, but also confers a decreased number of embryos available for transfer and embryo cryopreservation, so the cumulative clinical pregnancy rates are increased with cleavage stage transfer.[30] Transfer day two instead of day three after fertilisation has no differences in live birth rate.[30] There are significantly higher odds of preterm birth (odds ratio 1.3) and congenital anomalies (odds ratio 1.3) among births having from embryos cultured until the blastocyst stage compared with cleavage stage.[71]

In the UK, previous NICE guidelines defined infertility as failure to conceive after regular unprotected sexual intercourse for two years in the absence of known reproductive pathology.[11] Updated NICE guidelines do not include a specific definition, but recommend that "A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility, should be offered further clinical assessment and investigation along with her partner, with earlier referral to a specialist if the woman is over 36 years of age."[12]

Injectable medication cycle with IUI: If pregnancy doesn't result from ovulation induction with oral medications, the next step is to use injectable medications. These medications stimulate the ovaries to produce two to four eggs; when combined with IUI, you have an increased possibility of conception. Essentially, the sperm is given more targets to hit. You will come into the office for four to eight monitoring appointments to track egg development and cycle timing.
This is less extensively studied. It is not yet known whether the ovarian stimulation and the insemination have independent beneficial effects or whether their beneficial effects are only seen when they are used in combination. Most likely they both independently increase fertility potential, with relatively more fertility benefit coming from the IUI component.
Antisperm antibodies (ASA) have been considered as infertility cause in around 10–30% of infertile couples.[23] In both men and women, ASA production are directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, inhibiting capacitation and acrosome reaction, impaired fertilization, influence on the implantation process, and impaired growth and development of the embryo. The antibodies are classified into different groups: There are IgA, IgG and IgM antibodies. They also differ in the location of the spermatozoon they bind on (head, mid piece, tail). Factors contributing to the formation of antisperm antibodies in women are disturbance of normal immunoregulatory mechanisms, infection, violation of the integrity of the mucous membranes, rape and unprotected oral or anal sex. Risk factors for the formation of antisperm antibodies in men include the breakdown of the blood‑testis barrier, trauma and surgery, orchitis, varicocele, infections, prostatitis, testicular cancer, failure of immunosuppression and unprotected receptive anal or oral sex with men.[23][24]
Infertility can have a profound impact on one’s mental health. When men and women find out that they can’t conceive, they may experience the same painful emotions as anyone coping with grief or profound loss. Common reactions include shock, frustration, grief, anger, decreased self-esteem, anxiety, and depression, but feelings about infertility can vary greatly depending on the source of the problems. Men, in particular, find it far easier to deal with a partner’s infertility than with their own.
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis, is an autoimmune disorder causing inflammation of the thyroid gland. Hashimoto's thyroiditis is a type of hypothyroidism, and is the most common cause of hypothyroidism in the US. Symptoms of Hashimoto's thyroiditis may include dry skin, fatigue, weight gain, feeling cold, excessive sleepiness, dry skin, dry coarse hair, difficulty swallowing, a lump in the front of the throat, muscle cramps, mood changes, vague aches and pains, problems concentrating, leg swelling, constipation, and depression. There is no cure for Hashimoto’s thyroiditis. Diet changes, natural supplements, vitamins, or other natural products will not treat Hashimoto’s thyroiditis. Treatment for the autoimmune disorder is with thyroid hormone replacement therapy, which will be necessary for the rest of the person’s life.

Additionally, couples may turn to assisted reproductive technology, the most common of which is in vitro fertilization (IVF). Other techniques may include special injections or using a donor's eggs or sperm. Complications can sometimes occur, the most common being bleeding or infection; ovarian hyperstimulation syndrome, in which the ovaries become swollen and painful; and multiple pregnancies.
A 2013 review and meta analysis of randomised controlled trials of acupuncture as an adjuvant therapy in IVF found no overall benefit, and concluded that an apparent benefit detected in a subset of published trials where the control group (those not using acupuncture) experienced a lower than average rate of pregnancy requires further study, due to the possibility of publication bias and other factors.[34]
For many years, intrauterine insemination (IUI) was felt to be the best first choice of treatment in patients who have unexplained infertility or mild problems with the fallopian tubes or sperm. Arizona Reproductive Medicine (ARMS) has made significant advances in the cost effectiveness of in vitro fertilization (IVF) through higher IVF success rates and innovations in treatment medications and efficiency. IVF now far exceeds IUI as the best first choice of treatment for all age groups.
The diagnosis is one of exclusion — that is, one which is made only after all the existing tests have been performed and their results found to be normal. This is why the frequency of this diagnosis will depend upon how many tests are done by the clinic — the fewer the tests, the more frequent this diagnosis. And the better the tests, the more likely you are getting a diagnosis instead of being told it's "unexplained."
Apart from poor egg quality at advanced maternal age, older women are also less likely to respond to ovarian stimulation hormones that cause the release of multiple eggs. Being able to produce a dozen of eggs significantly increases the odds of success. It allows your fertility practitioner to choose the egg with normal genetic makeup and best likelihood of implantation. In both nature and IVF, not all eggs are suitable to produce a pregnancy. Ideally, you would produce 8-15 eggs after ovarian hyperstimulation so that some of them are genetically normal and perfectly matured.
Some research has found that IVF may raise the risk of some very rare birth defects, but the risk is still relatively low. Research has also found that the use of ICSI with IVF, in certain cases of male infertility, may increase the risk of infertility and some sexual birth defects for male children. This risk, however, is very low (less than 1%).
The best study in the field enrolled 750 women to receive clomid or letrozole, followed them for 5 courses of therapy and revealed that the group receiving letrozole had higher live birth rates and fewer multiple gestations. The data is of exceptional quality, and there’s no reason to believe the conclusion doesn’t also apply to the choice of drugs if these patients proceeded on to IUI.
IVF is a type of assisted reproductive technology used for infertility treatment and gestational surrogacy. A fertilised egg may be implanted into a surrogate's uterus, and the resulting child is genetically unrelated to the surrogate. Some countries have banned or otherwise regulate the availability of IVF treatment, giving rise to fertility tourism. Restrictions on the availability of IVF include costs and age, in order for a woman to carry a healthy pregnancy to term. IVF is generally not used until less invasive or expensive options have failed or been determined unlikely to work.
A genetic disorder. If you or your partner is at risk of passing on a genetic disorder to your child, you may be candidates for preimplantation genetic testing — a procedure that involves IVF. After the eggs are harvested and fertilized, they're screened for certain genetic problems, although not all genetic problems can be found. Embryos that don't contain identified problems can be transferred to the uterus.