Upwards of 30% of couples seeking fertility care are labeled with unexplained infertility. Given that over 50% of couples’ infertility struggles are at least partially attributable to the male, understanding the source of male infertility could allow for improved care. The limited set of male tests can only detect the major causes of infertility (i.e., azoospermia) leaving the less obvious factors invisible.
Endometriosis implants are most commonly found on the ovaries, the Fallopian tubes, outer surfaces of the uterus or intestines, and on the surface lining of the pelvic cavity. They also can be found in the vagina, cervix, and bladder. Endometriosis may not produce any symptoms, but when it does the most common symptom is pelvic pain that worsens just prior to menstruation and improves at the end of the menstrual period. Other symptoms of endometriosis include pain during sex, pain with pelvic examinations, cramping or pain during bowel movements or urination, and infertility. Treatment of endometriosis can be with medication or surgery.
One, two or three IVF treatments are government subsidised for women who are younger than 40 and have no children. The rules for how many treatments are subsidised, and the upper age limit for the women, vary between different county councils.[154] Single women are treated, and embryo adoption is allowed. There are also private clinics that offer the treatment for a fee.[155]
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.
^ Sher, KS; Jayanthi, V; Probert, CS; Stewart, CR; Mayberry, JF (1994). "Infertility, obstetric and gynaecological problems in coeliac sprue". Dig Dis. 12 (3): 186–90. doi:10.1159/000171452. PMID 7988065. There is now substantial evidence that coeliac sprue is associated with infertility both in men and women. (...) In men it can cause hypogonadism, immature secondary sex characteristics and reduce semen quality. (...) Hyperprolactinaemia is seen in 25% of coeliac patients, which causes impotence and loss of libido. Gluten withdrawal and correction of deficient dietary elements can lead to a return of fertility both in men and women.
However, the more you understand about what's coming next, the more in control you'll feel. While every clinic's protocol will be slightly different and treatments are adjusted for a couple's individual needs, here is a step-by-step breakdown of what generally takes place during in vitro fertilization, as well as information on the risks, costs, and what’s next if your IVF treatment cycle fails.
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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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.

The live birth rate is the percentage of all IVF cycles that lead to a live birth. This rate does not include miscarriage or stillbirth; multiple-order births, such as twins and triplets, are counted as one pregnancy. A 2017 summary compiled by the Society for Assisted Reproductive Technology (SART) which reports the average IVF success rates in the United States per age group using non-donor eggs compiled the following data:[10]

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.


The number to be transferred depends on the number available, the age of the woman and other health and diagnostic factors. In countries such as Canada, the UK, Australia and New Zealand, a maximum of two embryos are transferred except in unusual circumstances. In the UK and according to HFEA regulations, a woman over 40 may have up to three embryos transferred, whereas in the US, there is no legal limit on the number of embryos which may be transferred, although medical associations have provided practice guidelines. Most clinics and country regulatory bodies seek to minimise the risk of multiple pregnancy, as it is not uncommon for multiple embryos to implant if multiple embryos are transferred. Embryos are transferred to the patient's uterus through a thin, plastic catheter, which goes through her vagina and cervix. Several embryos may be passed into the uterus to improve chances of implantation and pregnancy.
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]

One, two or three IVF treatments are government subsidised for women who are younger than 40 and have no children. The rules for how many treatments are subsidised, and the upper age limit for the women, vary between different county councils.[154] Single women are treated, and embryo adoption is allowed. There are also private clinics that offer the treatment for a fee.[155]
Every woman is born with a set number of eggs, which declines as she ages. To get pregnant, an egg released from a woman’s ovaries must be fertilized by sperm, travel down the fallopian tube, and attach to the side of her uterus. At any stage along the way, a problem may occur, resulting in a case of infertility. For women, the most common causes of infertility are primary ovarian insufficiency (early menopause), ovulation disorders affecting egg release, uterine or cervical abnormalities, endometriosis (where tissue grows outside of the uterus), fallopian tube blockage or damage, polycystic ovary syndrome, and various hormonal imbalances. Certain cancers and their treatments can also negatively impact a woman’s fertility.
With egg donation and IVF, women who are past their reproductive years, have infertile male partners, have idiopathic female-fertility issues, or have reached menopause can still become pregnant. After the IVF treatment, some couples get pregnant without any fertility treatments.[3] In 2018, it was estimated that eight million children had been born worldwide using IVF and other assisted reproduction techniques.[4] However, a recent study that explores 10 adjuncts with IVF (screening hysteroscopy, DHEA, testosterone, GH, aspirin, heparin, antioxidants in males and females, seminal plasma, and PRP) suggests that until more evidence is done to show that these adjuncts are safe and effective, they should be avoided.[5]
^ 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.
Risk of multiples. IUI with fertility medication carries a significant risk of multiple pregnancies, including higher-order multiples (triplets or more). A good clinic will carefully monitor your follicles to make sure that only a safe number are mature before the IUI, but they cannot entirely eliminate the risk. Recent advances in IVF (including blastocyst transfer) mean that most modern fertility clinics now transfer only one or two embryos per IVF cycle. As a result, the risk of multiple pregnancies for IVF patients is much lower than it used to be.
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.
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.
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.

4. IVF or In-Vitro Fertilization - IVF means eggs are collected and fertilized outside the body, in a laboratory. This is followed by transferring the embryos into the uterus. This advanced technology has resulted in many successful pregnancies in women who had lost hope. During IVF - In-Vitro Fertilization, women can choose to freeze their healthy eggs for future use.

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.


^ Tersigni C, Castellani R, de Waure C, Fattorossi A, De Spirito M, Gasbarrini A, Scambia G, Di Simone N (2014). "Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms". Hum. Reprod. Update. 20 (4): 582–93. doi:10.1093/humupd/dmu007. PMID 24619876. Physicians should investigate women with unexplained infertility, recurrent miscarriage or IUGR for undiagnosed CD. (...) CD can present with several non-gastrointestinal symptoms and it may escape timely recognition. Thus, given the heterogeneity of clinical presentation, many atypical cases of CD go undiagnosed, leading to a risk of long-term complications. Among atypical symptoms of CD, disorders of fertility, such as delayed menarche, early menopause, amenorrhea or infertility, and pregnancy complications, such as recurrent abortions, intrauterine growth restriction (IUGR), small for gestational age (SGA) babies, low birthweight (LBW) babies or preterm deliveries, must be factored. (...) However, the risk is significantly reduced by a gluten-free diet. These patients should therefore be made aware of the potential negative effects of active CD also in terms of reproductive performances, and of the importance of a strict diet to ameliorate their health condition and reproductive health.

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]


Talk it out. Once you realize you’re entitled to your emotions, find an outlet for them. Talking about your feelings and your struggles can be a huge release and allow you to receive the support you need. If your family or friends don’t understand your sadness (or you find it hard to contain your baby envy around friends with more than one child), seek out people in your same situation. Find a support group for people with secondary infertility — online or in your area. And consider joining WTE's Trying to Conceive group to find moms who are also coping with secondary infertility.
PCOS: Polycystic ovarian syndrome (PCOS) is an ovarian issue that can cause irregular menstrual cycles and make it difficult for women to ovulate — a crucial part of the conception and pregnancy process. Women with PCOS do not release eggs regularly, and their ovaries often have many small cysts within. IVF is a strong option for women with PCOS, since it can help their bodies ovulate to achieve pregnancy.
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.
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. 

Fertilization. An embryologist (a scientist who specializes in eggs, sperm, and embryos) will examine your eggs before combining them with your partner's sperm and incubating them overnight. Fertilization usually happens during this time, but eggs that aren't normal may not be fertilized. (If sperm quality is poor, or if fertilization was unsuccessful during previous IVF cycles, your doctor may recommend using a technique called intracytoplasmic sperm injection (ICSI). With ICSI, a single sperm is injected directly into each mature egg.)


The treatment options for unexplained infertility are several and the treatment results are promising. Expectant management can be recommended if the woman is under 28-30 years of age and the infertility duration is less than 2-3 years. In vitro fertilization (IVF) has revolutionized the treatment of infertile couples, as well as profoundly increasing the basic understanding of human reproduction. IVF can be used as both a diagnostic and a therapeutic tool in couples with unexplained infertility. The pregnancy rates with IVF are good, at 40% per treatment cycle. In addition, the outcome of pregnancies among women with unexplained infertility is generally comparable to that of spontaneous and other pregnancies using assisted reproductive technologies.
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