It is possible that a significant contributor to unexplained infertility can be attributed to changes in sperm epigenetics. Methylation patterns in sperm DNA which affect the expression of various genes may be the missing link for this unique patient population. By employing epigenetic analysis, we may be able to identify more causes of infertility and suggest the optimal course of therapy. Preliminary evidence even suggests that these epigenetic signatures influence the probability of conception, embryogenesis, and successful carrying of pregnancy to term. Future research on sperm epigenetics holds the promise of revolutionizing reproductive medicine and empowering patients in the process.
First, consider where the information about the success rates is coming from. Generally speaking, IVF success rates in the United States comes from the clinics themselves or from the Center for Disease Control and Prevention. The Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine both contribute to the CDC data.
IVF is the most successful method of fertility treatment utilized today to help couples to conceive. The basic components of the IVF process include stimulation of the ovaries to produce multiple eggs at a time, removal of the eggs from the ovary (egg retrieval), fertilization of the eggs in the laboratory, and subsequent placement of the resulting embryos into the uterus (embryo transfer). The chance of pregnancy from IVF depends primarily on the age of the woman, the cause of infertility, and factors related to the quality of the IVF laboratory.

By 2017, many centers have adopted embryo cryopreservation as their primary IVF therapy, and perform few or no fresh embryo transfers. The two main reasons for this have been better endometrial receptivity when embryos are transferred in cycles without exposure to ovarian stimulation and also the ability to store the embryos while awaiting the results of pre-implantation genetic testing.
IVF is the most successful method of fertility treatment utilized today to help couples to conceive. The basic components of the IVF process include stimulation of the ovaries to produce multiple eggs at a time, removal of the eggs from the ovary (egg retrieval), fertilization of the eggs in the laboratory, and subsequent placement of the resulting embryos into the uterus (embryo transfer). The chance of pregnancy from IVF depends primarily on the age of the woman, the cause of infertility, and factors related to the quality of the IVF laboratory.
By 2017, many centers have adopted embryo cryopreservation as their primary IVF therapy, and perform few or no fresh embryo transfers. The two main reasons for this have been better endometrial receptivity when embryos are transferred in cycles without exposure to ovarian stimulation and also the ability to store the embryos while awaiting the results of pre-implantation genetic testing.

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.


For example, a deaf British couple, Tom and Paula Lichy, have petitioned to create a deaf baby using IVF.[99] Some medical ethicists have been very critical of this approach. Jacob M. Appel wrote that "intentionally culling out blind or deaf embryos might prevent considerable future suffering, while a policy that allowed deaf or blind parents to select for such traits intentionally would be far more troublesome."[100]

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.


Ovarian stimulation with hormonal medication is performed over a period of around 10-14 days. During this time, progress is monitored through ultrasound scans and blood tests. When enough oocytes (eggs) have developed in the ovaries, a final hormone injection triggers the maturing of the oocytes. Thirty-six hours later, egg retrieval is scheduled to take place in the fertility clinic.
In contrast, a study in 2016 compared outcomes of IVF and ICSI in patients with unexplained infertility and normal semen quality and showed promising results using ICSI 3. It was found that ICSI oocytes (84.5%) had a significantly higher fertilization rate compared to those inseminated by conventional IVF (67.6%). Moreover, there were no cases of complete fertilization failure (CFF) in the ICSI group, but CFF occurred in 7.9% of the IVF group.
When the ovarian follicles have reached a certain degree of development, induction of final oocyte maturation is performed, generally by an injection of human chorionic gonadotropin (hCG). Commonly, this is known as the "trigger shot."[67] hCG acts as an analogue of luteinising hormone, and ovulation would occur between 38 and 40 hours after a single HCG injection,[68] but the egg retrieval is performed at a time usually between 34 and 36 hours after hCG injection, that is, just prior to when the follicles would rupture. This avails for scheduling the egg retrieval procedure at a time where the eggs are fully mature. HCG injection confers a risk of ovarian hyperstimulation syndrome. Using a GnRH agonist instead of hCG eliminates most of the risk of ovarian hyperstimulation syndrome, but with a reduced delivery rate if the embryos are transferred fresh.[69] For this reason, many centers will freeze all oocytes or embryos following agonist trigger.
Although menopause is a natural barrier to further conception, IVF has allowed women to be pregnant in their fifties and sixties. Women whose uteruses have been appropriately prepared receive embryos that originated from an egg of an egg donor. Therefore, although these women do not have a genetic link with the child, they have a physical link through pregnancy and childbirth. In many cases the genetic father of the child is the woman's partner. Even after menopause the uterus is fully capable of carrying out a pregnancy.[109]
^ Jump up to: a b Moreton C (14 January 2007). "World's first test-tube baby Louise Brown has a child of her own". Independent. London. Retrieved 21 May 2010. The 28-year-old, whose pioneering conception by in-vitro fertilisation made her famous around the world. The fertility specialists Patrick Steptoe and Bob Edwards became the first to successfully carry out IVF by extracting an egg, impregnating it with sperm and planting the resulting embryo back into the mother
Fertility expert Zita West has noticed this increase at her London clinic. "The main reason," she explains, "is age. Women are having babies later." Exhaustion also plays a part. "The sleeplessness of life with a small child can't be underestimated," she says. "You might still be breastfeeding, you might be sharing a bed with a toddler, you might be holding down a job at the same time. Basically, there's not a lot of sex happening."
Advanced technologies add to your IVF bill but may also make a huge difference to your success rate. Pre-implantation genetic screening (PGS) can improve implantation rate by selectively transferring genetically normal embryos. For couples with male factor infertility, Intracytoplasmic sperm injection (ICSI) can help deliver a sperm directly into the egg. Nevertheless, ICSI only improves success rate in couples with severe male infertility.
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.
However, those percentages are from studies in which all the women had laparoscopy surgery to investigate the pelvic cavity for pelvic scarring and endometriosis. Laparoscopy surgery is no longer done as part of the routine fertility workup. Therefore, we are not finding all of the causes of infertility that we used to - leaving many more couples in the unexplained category.
The first successful birth of a child after IVF treatment, Louise Brown, occurred in 1978. Louise Brown was born as a result of natural cycle IVF where no stimulation was made. The procedure took place at Dr Kershaw's Cottage Hospital (now Dr Kershaw's Hospice) in Royton, Oldham, England. Robert G. Edwards was awarded the Nobel Prize in Physiology or Medicine in 2010, the physiologist who co-developed the treatment together with Patrick Steptoe and embryologist Jean Purdy; Steptoe and Purdy were not eligible for consideration as the Nobel Prize is not awarded posthumously.[1][2]
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.
Women are not always the source of a couple's infertility—in approximately one-third of cases, men may have difficulty with conception. In another third of cases, men are a contributing factor, along with female infertility and other problems. Men should be evaluated by a physician if there is a family history of infertility, if they have undergone cancer treatment, if they have small testicles, a swollen scrotum, or a low sperm count, or if they have any other testicular, prostate, or sexual problems.
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. 

The major complication of IVF is the risk of multiple births. This is directly related to the practice of transferring multiple embryos at embryo transfer. Multiple births are related to increased risk of pregnancy loss, obstetrical complications, prematurity, and neonatal morbidity with the potential for long term damage. Strict limits on the number of embryos that may be transferred have been enacted in some countries (e.g. Britain, Belgium) to reduce the risk of high-order multiples (triplets or more), but are not universally followed or accepted. Spontaneous splitting of embryos in the womb after transfer can occur, but this is rare and would lead to identical twins. A double blind, randomised study followed IVF pregnancies that resulted in 73 infants (33 boys and 40 girls) and reported that 8.7% of singleton infants and 54.2% of twins had a birth weight of less than 2,500 grams (5.5 lb).[35]
Today, with assisted-reproductive technology, the chance of successful treatment is very good. Intrauterine insemination with superovulation is the simplest approach since it increases the chances of the egg and sperm meeting, but some patients may also need GIFT and IVF. IVF can be helpful because it provides information about the sperm's fertilizing ability; GIFT, on the other hand, has a higher pregnancy rate and is applicable in these patients since they have normal fallopian tubes.
Success rates vary with the number of embryos transferred. However, transferring more and more embryos at one time does not increase the chance of live birth significantly, but may only increase the risk of a multiple pregnancy, and its associated risks. The impact of the number of embryos that are transferred also varies with the age of the woman.  
Using the information that you enter below, this tool allows you to estimate your chance of having a live birth using in vitro fertilization (IVF)—the most common type of Assisted Reproductive Technology (ART). This information is calculated based on the experiences of women and couples with similar characteristics. The estimates are based on the data we have available and may not be representative of your specific experience. Additionally, this IVF success estimator does not provide medical advice, diagnosis, or treatment. Please speak with your doctor about your specific treatment plan and potential for success.
The cost of an IUI is almost certainly less on a per cycle basis, but because IVF has much higher success rates and IUI is a poor option for some, the higher per cycle cost of IVF can actually be more affordable in the long run – in terms of the cost to bring home a baby.  Because most successful IUIs happen in the first three or four-cycle, it eventually becomes very expensive to bring home a baby with an IUI.
For example, a deaf British couple, Tom and Paula Lichy, have petitioned to create a deaf baby using IVF.[99] Some medical ethicists have been very critical of this approach. Jacob M. Appel wrote that "intentionally culling out blind or deaf embryos might prevent considerable future suffering, while a policy that allowed deaf or blind parents to select for such traits intentionally would be far more troublesome."[100]
If both partners are young and healthy and have been trying to conceive for one year without success, a visit to a physician or women's health nurse practitioner (WHNP) could help to highlight potential medical problems earlier rather than later. The doctor or WHNP may also be able to suggest lifestyle changes to increase the chances of conceiving.[62]
Many people have never heard the term "secondary infertility"; fewer understand it. I discovered it a year into my struggle to conceive a second child and fell on it, amazed. What I was undergoing had a name! I wrote it down and immediately felt better, as if the phrase exuded a talismanic power that might protect me from the likes of my neighbour.

In July 1978, Louise Brown was the first child successfully born after her mother received IVF treatment. Brown was born as a result of natural-cycle IVF, where no stimulation was made. The procedure took place at Dr Kershaw's Cottage Hospital (now Dr Kershaw's Hospice) in Royton, Oldham, England. Robert G. Edwards was awarded the Nobel Prize in Physiology or Medicine in 2010. The physiologist co-developed the treatment together with Patrick Steptoe and embryologist Jean Purdy but the latter two were not eligible for consideration as they had died and the Nobel Prize is not awarded posthumously.[1][2]
Anger, sadness, and anxiety are common among parents struggling to expand their family. "Having a child already doesn't make going through infertility any easier," says Alice D. Domar, Ph.D., executive director of the Domar Center for Mind/Body Health, in Waltham, Massachusetts, and author of Conquering Infertility. Meeting with a mental-health professional or seeking out blogs and online groups for secondary infertility can help. The website of  the National Infertility Association, resolve.org, is a good place to start.
Studies have indicated that IVF mothers show greater emotional involvement with their child, and they enjoy motherhood more than mothers by natural conception. Similarly, studies have indicated that IVF father's express more warmth and emotional involvement than fathers by adoption and natural conception and enjoy fatherhood more. Some IVF parents become overly involved with their children.[136]
Fertility expert Zita West has noticed this increase at her London clinic. "The main reason," she explains, "is age. Women are having babies later." Exhaustion also plays a part. "The sleeplessness of life with a small child can't be underestimated," she says. "You might still be breastfeeding, you might be sharing a bed with a toddler, you might be holding down a job at the same time. Basically, there's not a lot of sex happening."
The Rand Consulting Group has estimated there to be 400,000 frozen embryos in the United States in 2006.[83] The advantage is that patients who fail to conceive may become pregnant using such embryos without having to go through a full IVF cycle. Or, if pregnancy occurred, they could return later for another pregnancy. Spare oocytes or embryos resulting from fertility treatments may be used for oocyte donation or embryo donation to another woman or couple, and embryos may be created, frozen and stored specifically for transfer and donation by using donor eggs and sperm. Also, oocyte cryopreservation can be used for women who are likely to lose their ovarian reserve due to undergoing chemotherapy.[84]

^ Manheimer E, van der Windt D, Cheng K, Stafford K, Liu J, Tierney J, Lao L, Berman BM, Langenberg P, Bouter LM (2013). "The effects of acupuncture on rates of clinical pregnancy among women undergoing in vitro fertilization: a systematic review and meta-analysis". Human Reproduction Update. 19 (6): 696–713. doi:10.1093/humupd/dmt026. PMC 3796945. PMID 23814102.


Nadya Suleman came to international attention after having twelve embryos implanted, eight of which survived, resulting in eight newborns being added to her existing six-child family. The Medical Board of California sought to have fertility doctor Michael Kamrava, who treated Suleman, stripped of his licence. State officials allege that performing Suleman's procedure is evidence of unreasonable judgment, substandard care, and a lack of concern for the eight children she would conceive and the six she was already struggling to raise. On 1 June 2011 the Medical Board issued a ruling that Kamrava's medical licence be revoked effective 1 July 2011.[116][117] [118]
Infertility is “a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse (and there is no other reason, such as breastfeeding or postpartum amenorrhoea). Primary infertility is infertility in a couple who have never had a child. Secondary infertility is failure to conceive following a previous pregnancy. Infertility may be caused by infection in the man or woman, but often there is no obvious underlying cause.

The AMIGOS study suggested that clomid provided the best balance of a high pregnancy rate with a reasonably low multiple rate among couples with unexplained infertility. However, the authors of the Huang study concluded that on balance letrozole was better. From our vantage point, given that clomid more commonly causes multiple eggs to be ovulated, it seems like the slightly better option between the two because the whole point of treatment in unexplained infertility patients is to increase the odds of delivery by increasing the number of eggs ovulated.
Along with being physically demanding, fertility treatments can also spark a roller-coaster of emotions each month, including hope, anger, disappointment, sadness, and guilt. Just the sight of a pregnant woman can evoke strong negative and stressful feelings. During this time, those struggling with infertility may pull away from friends and family who remind them of their difficulty with reproduction; some of their closest relationships may suffer.
×