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.
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.
Very slight elements of risk are associated with any medical intervention but for IVF the most notable risk in the past has been multiple births. The impact of multiple births on birth weight, premature delivery, and post-natal complications is well known. This is largely due to the practice over the past 30 years of transferring two or more embryos during IVF. Thanks to PGT-A testing and Single Embryo Transfer (SET), however, doctors can now feel confident about transferring just one normal embryo. At RMA, we have established SET as the standard of care going forward. With SET, the risk of multiple births is drastically reduced.
Sunni Muslim nations generally allow IVF between married couples when conducted with their own respective sperm and eggs, but not with donor eggs from other couples. But Iran, which is Shi'a Muslim, has a more complex scheme. Iran bans sperm donation but allows donation of both fertilised and unfertilised eggs. Fertilised eggs are donated from married couples to other married couples, while unfertilised eggs are donated in the context of mut'ah or temporary marriage to the father.[176]
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.

Primary infertility is defined as the absence of a live birth for women who desire a child and have been in a union for at least 12 months, during which they have not used any contraceptives.[14] The World Health Organisation also adds that 'women whose pregnancy spontaneously miscarries, or whose pregnancy results in a still born child, without ever having had a live birth would present with primarily infertility'.[14]
For cases where donor sperm is required, the majority of patients use commercial sperm banks as their source of donor sperm. You can find out a lot about a potential donor before making your choice. For example, you can access information about the donor’s ethnic or racial background, education, and physical characteristics. It’s also reassuring to know that sperm banks always screen donors for sexually transmitted diseases (STDs) such as chlamydia, syphilis, gonorrhea, hepatitis, HIV, and others. The FDA and the Centers for Disease Control and Prevention (CDC) recommend that frozen semen from a licensed sperm bank be used in order to prevent STDs.
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. Copyright 1997-2020, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM Health Solutions.
There are multiple strategies for causing ovulation in clomid or letrozole resistant patients. Some of these include adding medications such as dexamethasone or metformin to the treatment regimen. Another approach is changing to gonadotropin injections. Rather than tricking the brain into sending a stronger signal to the ovaries to cause follicle recruitment, gonadotropins directly stimulate the ovary to recruit multiple follicles.
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.

Addressing lifestyle issues is not meant to be a quick fix, and typically does not lead to instant success. However, with unexplained infertility every little bit counts, so don’t fret or give up. Do not assume just because the cause of infertility is unexplained, it is untreatable or there is no pathway to parenthood. When a specific cause is not determined for women, and male infertility has also been ruled out, our fertility specialist may begin a course of treatment to improve the chances of conception and pregnancy. The speed with which interventions are offered depends on each individual’s own needs and desires as determined by age and other factors.
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.
During the second half of your menstrual cycle, the hormone progesterone kicks in to help prepare the lining of your uterus for a fertilized egg. If the egg isn't fertilized and doesn't implant, it disintegrates, progesterone levels fall, and about 12 to 16 days later, the egg -- along with blood and tissues from the lining of the uterus -- is shed from the body. That process is menstruation. It usually lasts 3 to 7 days.
Women who switch from IUI to IVF sooner or begin with IVF get pregnant quicker than those who stick or start with IUI. One study found that undergoing immediate IVF resulted in superior pregnancy rates with fewer treatment cycles compared to those who did two rounds of IUI before switching to IVF.  While the immediate IVF group got pregnant quicker, the overall success after up to 6 IVF cycles was similar.
Step on the scale. Have you put on some extra pounds since your last baby was on board? Or maybe you’ve lost a lot of weight (because after all, who has time to eat when you’re running after a little one)? Your weight can impact your fertility, so getting as close as possible to a healthy BMI can also help get you closer to that second pregnancy you’re hoping for.
For couples who have no difficulty achieving a pregnancy, the natural chance of pregnancy per month of ovulation is largely dependent on the age of the woman. For women in their early 30s or younger, the natural pregnancy rate is about 20 to 25 percent per cycle. This drops off significantly through her mid-to late-30s; by her early 40s, the chance of pregnancy is about 5 percent per cycle. This age-related decrease is primarily due to a decline in the quality of the eggs within the ovaries.

Unlike the simpler process of artificial insemination -- in which sperm is placed in the uterus and conception happens otherwise normally -- IVF involves combining eggs and sperm outside the body in a laboratory. Once an embryo or embryos form, they are then placed in the uterus. IVF is a complex and expensive procedure; only about 5% of couples with infertility seek it out. However, since its introduction in the U.S. in 1981, IVF and other similar techniques have resulted in more than 200,000 babies.
1. Changes to Your Menstrual Cycle: This may be an absence of your period, heavier than normal flow or irregular menstrual cycles may be signs of infertility. Consider tracking your menstrual cycle to help you identify patterns or changes early on. This will also be helpful in case you ever seek guidance from a physician, as he or she will inquire about your medical history.
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]
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 first step in finding the right treatment is to find out if there is an actual cause for unexplained infertility. Taking treatment helps to increase the chances of conceiving, and also makes it likelier that you will get pregnant sooner. The treatment of luteal-phase defects is as controversial as the diagnosis. They can be treated by using clomiphene, which may help by augmenting the secretion of FSH and thus improving the quality of the follicle (and therefore, the corpus luteum, which develops from it). Direct treatment with progesterone can also help luteal-phase abnormalities. Progesterone can be given either as injections or vaginal suppositories.
Fertility was found to be a significant factor in a man's perception of his masculinity, driving many to keep the treatment a secret.[139] In cases where the men did share that he and his partner were undergoing IVF, they reported to have been teased, mainly by other men, although some viewed this as an affirmation of support and friendship. For others, this led to feeling socially isolated.[140] In comparison with women, men showed less deterioration in mental health in the years following a failed treatment.[141] However many men did feel guilt, disappointment and inadequacy, stating that they were simply trying to provide an 'emotional rock' for their partners.[140]
For women, intake of antioxidants (such as N-acetyl-cysteine, melatonin, vitamin A, vitamin C, vitamin E, folic acid, myo-inositol, zinc or selenium) has not been associated with a significantly increased live birth rate or clinical pregnancy rate in IVF according to Cochrane reviews.[30] The review found that oral antioxidants given to men in couples with male factor or unexplained subfertility may improve live birth rates, but more evidence is needed.[30]
^ 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
Our specialized team of andrologists prepare each sperm sample with a procedure commonly known as "sperm washing" in one of our andrology laboratories. Sperm washing involves placing the sperm sample in a test tube and then a centrifuge, which results in the sperm collecting in a "pellet" at the bottom of the test tube. The andrologist removes the seminal fluid and places the fluid (media) above the sperm. The most active sperm will then swim up into the media. The final sample consists of the most active sperm concentrated in a small volume of media. A single IUI is usually performed when a patient is using fresh sperm. If a patient is using a frozen sperm sample, the clinician can likely perform one or two IUIs.
A recent controversy in California focused on the question of whether physicians opposed to same-sex relationships should be required to perform IVF for a lesbian couple. Guadalupe T. Benitez, a lesbian medical assistant from San Diego, sued doctors Christine Brody and Douglas Fenton of the North Coast Women's Care Medical Group after Brody told her that she had "religious-based objections to treating her and homosexuals in general to help them conceive children by artificial insemination," and Fenton refused to authorise a refill of her prescription for the fertility drug Clomid on the same grounds.[111][112] The California Medical Association had initially sided with Brody and Fenton, but the case, North Coast Women's Care Medical Group v. Superior Court, was decided unanimously by the California State Supreme Court in favour of Benitez on 19 August 2008.[113][114]
Time. The factor of time cuts both ways when you are weighing up these two options. IUI is a much shorter process than IVF, so if your first cycle is successful, it could be the quickest route to bringing home a baby. However, because of the gap in success rates between the two treatments, some patients in their late 30s to early 40s may get pregnant faster by going directly to IVF rather than waiting until they have had several failed IUI cycles.
Certain kinds of IVF, in particular ICSI (first applied in 1991) and blastocyst transfer (first applied in 1984) have been shown to lead to distortions in the sex ratio at birth. ICSI leads to slightly more female births (51.3% female) while blastocyst transfer leads to significantly more boys (56.1% male) being born. Standard IVF done at the second or third day leads to a normal sex ratio.
If a man and woman 35 or younger have had unprotected sex for at least 12 months (or six months if older than 35) without getting pregnant, they should suspect secondary infertility. This especially applies to women older than 30 who have experienced pelvic inflammatory disease, painful periods, irregular menstrual cycles or miscarriages, and to men with low sperm counts.
^ Hozyasz, K (March 2001). "Coeliac disease and problems associated with reproduction". Ginekol Pol. 72 (3): 173–9. PMID 11398587. Coeliac men may have reversible infertility, and as in women, if gastrointestinal symptoms are mild or absent the diagnosis may be missed. It is important to make diagnosis because the giving of gluten free diet may result in conception and favourable outcome of pregnancy.
When you face secondary infertility, you’re dealing not only with the typical ups and downs of TTC, but also with the additional emotional fallout that is unique to those having difficulty getting pregnant with baby number two. In addition to feeling disappointed and upset, you may also be feeling shock (“I got pregnant so easily the first time, there’s no way I could have infertility problems”), guilt (“I already have a child, so I should be happy”) and even isolation (“I can’t connect with the people facing primary infertility and I can’t connect with my friends who have multiple kids”). How do you reconcile these conflicting emotions — and how do you tackle them while trying to raise the child you already have?

If you're not pregnant, you'll stop taking progesterone and likely get your period within a week. If you don't get your period or you have unusual bleeding, contact your doctor. If you're interested in attempting another cycle of in vitro fertilization (IVF), your doctor might suggest steps you can take to improve your chances of getting pregnant through IVF.


For any woman or couple facing infertility, the task of deciding on your next steps can feel very daunting. Of course, there’s no substitute for the advice of a fertility specialist, but a general idea of what to expect can help give you confidence. You might be wondering what is the difference between In Vitro Fertilization (IVF) and  IUI, or artificial insemination?

Fertilization of the oocytes must happen with 12 to 24 hours. Your partner will likely provide a semen sample the same morning you have the retrieval. The stress of the day can make it difficult for some, and so just in case, your partner may provide a semen sample for backup earlier in the cycle, which can be frozen until the day of the retrieval.
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.
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.
IVF may be used to overcome female infertility when it is due to problems with the fallopian tubes, making in vivo fertilisation difficult. It can also assist in male infertility, in those cases where there is a defect in sperm quality; in such situations intracytoplasmic sperm injection (ICSI) may be used, where a sperm cell is injected directly into the egg cell. This is used when sperm has difficulty penetrating the egg. In these cases the partner's or a donor's sperm may be used. ICSI is also used when sperm numbers are very low. When indicated, the use of ICSI has been found to increase the success rates of IVF.

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.
Use our website links to find your nearest clinic, or fill out our online contact form. You may want to discuss the pros and cons of IUI and IVF or you may just want to explore all the options that might be available. The sooner you take that first step to discuss your fertility issues with one of our physicians, the sooner you can decide on the next step in your fertility journey and take one step closer to achieving your dream of holding your own new baby in your arms.
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. Copyright 1997-2020, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM Health Solutions.
Deciding whether to undergo in vitro fertilization, and how to try if the first attempt is unsuccessful, is an incredibly complicated decision. The financial, physical, and emotional toll of this process can be difficult. Speak with your doctor extensively to determine what your best options are and if in vitro fertilization is the right path for you and your family. Seek a support group or counselor to help you and your partner through this process.
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.
There is no one-size-fits-all solution to infertility, and the path you take will be unique to your specific case, but there are some common starting points. Intrauterine insemination (IUI) and in vitro fertilization (IVF) are two of the most popular infertility treatments available today. Understanding what they are, who they are intended for, and what the success rates are for these two options will give you a place to begin your conversations with your fertility expert. Here’s what you need to know.
Amongst these two patient populations (which we’ll refer to now as PCOS), IUI with clomid and letrozole generally shows no improvement versus when these drugs are taken without IUI. When IUI is coupled with gonadotropins, success rates reach 14 - 26% per cycle, which is higher than almost any other patient class, but still pales in comparison to IVF. It’s also worth noting that PCOS patients who are taking gonadotropins have a very high risk of multiples.

A recent large population-based study collected data from almost 5000 European patients. According to preliminary results presented at the 2019 European Society of Human Reproduction and Embryology, there is no benefit from ICSI in non-male factor cases. Importantly, the study reported no benefit of using ICSI regardless of how many eggs are retrieved after ovarian stimulation. Therefore, having a low oocyte yield should not be a reason for choosing ICSI over IVF.
Clomiphene citrate (Clomid, Serophene) is a medication commonly used for the treatment of women with ovulation disorders as reflected by infrequent or irregular menstrual cycles. Clomid is a pill taken orally for 5 to 7 days, typically on day 3 of a woman’s menstrual cycle to induce ovulation. Clomid works at the level of the brain and pituitary gland and facilitates the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH, in turn, stimulate the ovaries to produce eggs and the ovarian hormones estradiol (E2) and progesterone (P4). The initial prescribed dosage of clomid is 50 to 100 mg (one or two tablets) daily at bedtime, or as prescribed by your physician.

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.

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]


Another major cause of infertility in women may be the inability to ovulate. Malformation of the eggs themselves may complicate conception. For example, polycystic ovarian syndrome is when the eggs only partially develop within the ovary and there is an excess of male hormones. Some women are infertile because their ovaries do not mature and release eggs. In this case synthetic FSH by injection or Clomid (Clomiphene citrate) via a pill can be given to stimulate follicles to mature in the ovaries.
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]
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.
Previous tests should be carefully reviewed to ensure that the diagnosis is, in fact, "unexplained," and that no test has been omitted or missed. It may sometimes be necessary to repeat certain investigations. For example, if a previous laparoscopy has been done by a single puncture and reported as normal, it may be necessary to repeat the laparoscopy with a double puncture, to look for early endometriosis. 
Assisted hatching. About five to six days after fertilization, an embryo "hatches" from its surrounding membrane (zona pellucida), allowing it to implant into the lining of the uterus. If you're an older woman, or if you have had multiple failed IVF attempts, your doctor might recommend assisted hatching — a technique in which a hole is made in the zona pellucida just before transfer to help the embryo hatch and implant. Assisted hatching is also useful for eggs or embryos that have been previously frozen as the process can harden the zona pellucida.
Are you infertile, or just having trouble getting pregnant? If you go to the doctor, here’s how a diagnosis of infertility will happen. “Infertility” is a term that describes when a couple is unable to conceive a child after a year of having sex without birth control. In women who are older than age 35, infertility… Read More »How Doctors Diagnose Infertility
3-6 months of treatment with Clomid pills (clomiphene citrate) might improve fertility by as much as 2 times as compared to no treatment. This is a very low level infertility treatment. Infertility specialists do not usually recommend Clomid treatment( without insemination) for unexplained infertility for women over the age of about 35. Most fertility specialists do not use it (without IUI) on any couples with unexplained infertility. If a woman is already having regular periods and ovulating one egg every month, giving Clomid, which will probably stimulate the ovaries to release 2 or 3 eggs per month (instead of one) is not really fixing anything that is broken - and is not likely to be successful.
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