What is Normal Fertility and When Does it Become Infertility?
What is Infertility?
Most people will have the strong desire to conceive a child at some point during their lifetime. Understanding what defines normal fertility is crucial to helping a person, or couple, know when it is time to seek help. Most couples (approximately 85%) will achieve pregnancy within one year of trying, with the greatest likelihood of conception occurring during the earlier months. Only an additional 7% of couples will conceive in the second year. As a result, infertility has come to be defined as the inability to conceive within 12 months. This diagnosis is therefore shared by 15% of couples attempting to conceive. We generally recommend seeking the help of a reproductive endocrinologist if conception has not occurred within 12 months. However, there are various scenarios where one may be advised to seek help earlier. These include:
- Infrequent menstrual periods: When a woman has regular menstrual periods, defined as regular cycles occurring every 21 to 35 days, this almost always indicates that she ovulates regularly. Ovulation of the egg occurs approximately 2 weeks before the start of the next period. If a woman has cycles at intervals of greater than 35 days, it may indicate that she is not ovulating an egg predictably, or even at all. Ovulation of the egg is essential for pregnancy. Therefore, we recommend an evaluation if menstrual cycles are infrequent or irregular in a couple attempting pregnancy.
- Female age of 35 years or older: For unclear reasons, egg numbers decrease at a rapid rate as women age. Furthermore, as aging occurs, egg quality, or the likelihood of an egg being genetically normal, decreases. Therefore we recommend a fertility evaluation if a couple has been attempting pregnancy for 6 months or more when the woman is 35 years of age or older.
- A history of pelvic infections or sexually transmitted diseases: Sexually transmitted infections, such as chlamydia or gonorrhea, can cause inflammation and permanent scarring of the fallopian tubes. The presence of open tubes is essential for natural conception, as sperm must traverse the tubes in order to reach and fertilize the ovulated egg. We recommend immediate evaluation for a couple attempting pregnancy when the woman has a prior history of pelvic infection. As part of the fertility evaluation, we will perform an HSG, a test designed to evaluate if the fallopian tubes are open.
- Known uterine fibroids or endometrial polyps: Uterine abnormalities, such as fibroids that indent the endometrial cavity and endometrial polyps, can impair how the endometrium (the lining of the uterus) and embryo interact to lower implantation and pregnancy rates. These abnormalities can also cause irregular bleeding between menstrual cycles. Evaluation should be pursued by 6 months of attempted pregnancy in women with a known history of these abnormalities or a history of bleeding between menstrual cycles. The main approach to correcting or removing these uterine abnormalities is by hysteroscopy, a surgical method by which a narrow scope with a camera is placed within the uterine cavity. Instruments can be introduced through the hysteroscope, allowing the surgeon to remove or correct any anatomic abnormalities.
- Known male factor semen abnormalities: If a male partner has a history of infertility with a prior partner, or if there are abnormalities on his semen analysis, then we advise earlier fertility evaluation, ideally within 6 months of attempting pregnancy.
What is Involved in the Fertility Evaluation?
History and physical examination – First and foremost, your fertility physician will take a very thorough medical and fertility history. Your doctor may ask you many of the following questions: How long have you been trying to get pregnant? How often are you having intercourse? Do you have pain with menstrual periods or intercourse? Have you been pregnant before? What happened with your prior pregnancies? Have you had any sexually transmitted infections or abnormal pap smears? How often do you have menstrual cycles? Do you have any medical problems or prior surgeries? Do you have a family history of medical problems? These and many other questions will help your physician design a specific evaluation and potential treatment for you. In addition to a careful history, a physical evaluation may also be performed.
Transvaginal ultrasound – Ultrasound is an important tool in evaluating the structure of the uterus, tubes, and ovaries. Ultrasound can detect uterine abnormalities such as fibroids and polyps, distal fallopian tube occlusion, and ovarian abnormalities including ovarian cysts. Additionally, transvaginal ultrasound affords the opportunity for your physician to assess the relative number of available eggs. This measurement is called the antral follicle count and may correlate with fertility potential.
Laboratory testing – Depending on the results of the evaluation discussed above, your physician may request specific blood tests. The most common of these tests include measurements of blood levels of certain hormones such as estradiol and FSH, which are related to ovarian function and overall egg numbers; TSH, which assesses thyroid function; and prolactin, a hormone that can affect menstrual function if elevated.
Hysterosalpingogram (HSG) – This test is essential for evaluating fallopian tubal patency, uterine filling defects such as fibroids and polyps, and scarring of the uterine cavity (Asherman syndrome). Many uterine and tubal abnormalities detected by the HSG can be surgically corrected.
Semen analysis – The semen analysis is the main test to evaluate the male partner. There are four parameters analyzed: 1) semen volume – should be at least 1.5 to 2 ml. A smaller amount may suggest a structural or hormonal problem leading to deficient semen production; 2) sperm concentration – normal concentration should be at least 20 million sperm per 1 ml of semen. A lower concentration may lead to a lower chance for conception without treatment; 3) sperm motility or movement – a normal motility should be at least 50%. Less than 50% motility may significantly affect the ability for sperm to fertilize the egg without therapy; and (4) morphology, or shape – there are three parts of the sperm that are analyzed for morphology: the head, midpeice, and tail. Abnormality in any of those regions may indicate abnormal sperm function and compromise the ability of sperm to fertilize the egg. Ideally, using strict morphology criteria, a minimum of 5 – 15% normal forms leads to a better ability for sperm to fertilize the egg. An abnormal semen analysis warrants a further evaluation usually by a reproductive urologist. Your physician will refer you to a reproductive urologist if appropriate.
What are the Common Causes of Infertility?
What Causes Infertility?
1) Advancing maternal age: Historically before the latter 20th century, women were conceiving in their teens and twenties, when age-related abnormalities with the egg were not evident. However, in our modern era, women are delaying child birth until their thirties and forties, which has lead to the discovery of the adverse effect of advanced maternal age on egg function. In fact, female age-related infertility is the most common cause of infertility today. For unknown reasons, as women age, egg numbers decrease at a rapid rate. And as aging occurs, egg quality, or the likelihood of an egg being genetically normal, decreases as well. Hence the ability to conceive a normal pregnancy decreases from when a woman is in her early 30s into her 40s. A woman is rarely fertile beyond the age of 45. This applies to the ability to conceive with her eggs, but not with donor eggs.
2) Ovulation disorders: Normal and regular ovulation, or release of a mature egg, is essential for women to conceive naturally. Ovulation often can be detected by keeping a menstrual calendar or using an ovulation predictor kit. There are many disorders that may impact the ability for a woman to ovulate normally. The most common disorders impacting ovulation include polycystic ovary syndrome (PCOS), hypogonadotropic hypogonadism (from signaling problems in the brain), and ovarian insufficiency (from problems of the ovary). If your cycles are infrequent or irregular, your doctor will examine you and perform the appropriate testing to discover which problem you may have and present the appropriate treatment options.
3) Tubal occlusion (blockage): As discussed previously, a history of sexually transmitted infections including chlamydia, gonorrhea, or pelvic inflammatory disease can predispose a woman to having blocked fallopian tubes. Tubal occlusion is a cause of infertility because an ovulated egg is unable to be fertilized by sperm or to reach the endometrial cavity. If both tubes are blocked, then in vitro fertilization (IVF) is required. If a tube is blocked and filled with fluid (called a hydrosalpinx), then minimally invasive surgery (laparoscopy or hysteroscopy) to either remove the tube or block/separate it from the uterus prior to any fertility treatments is recommended.
4) Uterine fibroids: Fibroids are very common (approximately 40% of women may have them) and the mere presence alone does not necessarily cause infertility. There are three types of fibroids: 1) subserosal, or fibroids that extend more than 50% outside of the uterus; 2) intramural, where the majority of the fibroid is within the muscle of the uterus without any indentation of the uterine cavity; and 3) submucosal, or fibroids the project into the uterine cavity. Submucosal fibroids are the type if fibroid that has clearly been demonstrated to reduce pregnancy rate, roughly by 50%, and removal of which will double pregnancy rate. In some cases, simply removing the submucosal fibroid solves infertility. Often, but not always, submucosal fibroids can cause heavy periods, or bleeding between periods. There is more controversy regarding intramural fibroids, where larger ones may have an impact and may necessitate removal. Subserosal fibroids do not affect pregnancy. Your physician will examine you carefully to determine if you have fibroids and if removal is necessary.
5) Endometrial polyps: Endometrial polyps are finger-like growths in the uterine cavity arising from the lining of the uterus, called the endometrium, These abnormalities are rarely associated with cancer (<1% in a woman before menopause), but polyps are can decrease fertility by up to 50% according to some studies. Removal of polyps by the minimally invasive procedure hysteroscopy is associated with a doubling of pregnancy rate. In some cases, simply removing the polyp solves infertility.
6) Male factors affecting sperm function: Male factor infertility has been associated as a contributing factor causing infertility in 40-50% percent of cases, and as the sole cause for infertility in 15-20% percent of cases. If a semen analysis is found to be abnormal, generally it is first repeated to confirm the abnormality. Once confirmed, the male partner is referred to a reproductive urologist, especially if the abnormality is severe. In some cases, the reproductive urologist can improve semen function by recommending certain lifestyle changes, by hormonal treatments, or by surgery. In most cases however, sperm function may not improve and therefore any attempts at pregnancy may require additional treatments or procedures performed by our clinic. Options include intrauterine insemination (also known as IUI) or IVF with intracytoplasmic sperm injection (also known as ICSI).
A. Intrauterine insemination is a process by which sperm is washed and prepared for placement into the uterine cavity, therefore bypassing the cervix and bringing a higher concentration of motile sperm closer to the tubes and ovulated egg. At least one open tube is required for IUI, and the sperm abnormality cannot be severe otherwise the sperm will not be able to swim to and fertilize the egg.
B. Intracytoplasmic sperm injection is a process by which semen is washed and prepared for direct injection of one sperm into each egg collected during the IVF process. In order to perform ICSI, an egg is held via a small suction pipette, while one sperm is injected into that egg using a very fine glass needle. This process bypasses the normal fertilization process, which may be compromised due to poor sperm function. Your doctor will analyze your semen analysis carefully and help you decide if ICSI is an appropriate treatment for you.
7) Endometriosis: Endometriosis is a condition whereby cells very similar to the ones lining the uterine cavity, or endometrium, are found outside the uterine cavity. It is found in approximately 10-50% of reproductive-aged women and can be associated with infertility as well as pain during intercourse and/or menstrual periods. Endometriosis causes infertility by producing inflammation and scarring, which can result in not only pain but also potentially detrimental effects on egg, sperm or embryo. Endometriosis can only be confirmed by surgery, usually laparoscopy. If endometriosis is found, it can be surgically removed by various methods, and its removal may lead to a decrease in pain as well as improvement in the ability to conceive naturally. Your doctor will determine if you are at risk of having endometriosis based on a careful history, physical exam, and ultrasound.
8) Unexplained/other: Sometimes a full evaluation does not reveal the cause of infertility. This occurs approximately 15% of the time. Thankfully, even when the cause of infertility is not known, various fertility treatments can overcome the unknown road block that was preventing pregnancy and eventually lead to delivery of a healthy baby.
What are the Treatment Options?
Treatment for Infertility
1) Education: We strongly believe that educating our patients about the normal process of fertility, problems that affect fertility, and treatment options will empower our patients to make the best choices. Understanding the normal reproductive process is essential in knowing when to seek help. Helping our patients develop a deep understanding of their fertility options will make the process smoother. Our goal is to have each and every patient feel as part of our team, a team that is focused on helping them have a healthy baby. For those interested, we offer a free class entitled, “The Couple’s Guide to IVF”, that meets twice monthly and is open to the public.
2) Medications to induce egg development and ovulation: The medications that help stimulate the ovary to develop mature eggs for ovulation come in two forms: pills taken by mouth and injections. The most commonly prescribed pill to stimulate ovulation (generally of one mature egg) is clomiphene citrate. This pill generally is taken from menstrual cycle days 3 – 7. It works in the following way: Clomiphene is an anti-estrogen. It binds in a part of the brain called the hypothalamus, which is essential in stimulating the ovary to grow and release an egg. When clomiphene binds to estrogen receptors in the hypothalamus, it leads to an increase release of an important signaling hormone called GnRH (gonadotropin releasing hormone). This hormone then binds to another area of the brain called the pituitary gland and leads to the release of FSH (follicle stimulating hormone), a hormone that directly binds to cells in the ovary, leading to egg growth and maturation.
The most commonly prescribed injections that stimulate the ovary are called gonadotropins. The gonadotropins in these formulations are FSH, and in some cases, a combination of FSH and LH (luteinizing hormone). These injections are taken nightly, typically for 5 – 10 days, and act directly on the cells of the ovary to stimulate egg development. Once a follicle containing an egg reaches a mature size, another hormone injection called HCG is often given to mimic the natural LH surge that occurs at the time of ovulation. This leads to the final maturation and release of the egg.
3) Insemination: Intrauterine insemination, also known as IUI, is a process by which sperm is washed and prepared for placement into the uterine cavity, therefore bypassing the cervix and bringing a higher concentration of motile sperm closer to the tubes and ovulated egg. In order to accomplish this, the semen is washed with a solution safe to sperm and eggs, and then centrifuged to separate motile sperm from immotile sperm and other cells. Those motile and viable sperm are then placed in a very small amount of solution, and then very gently and painlessly injected into the uterine cavity using a very thin, soft, and flexible catheter. At least one open tube is required for IUI, and any sperm abnormality cannot be severe, otherwise the sperm will not be able to swim to and fertilize the egg.
4) In Vitro Fertilization (IVF): In vitro means “outside the body.” IVF is a process whereby eggs are collected and then fertilized by sperm outside the body, in an embryology laboratory. The first IVF baby was born in 1978 in England. Not long after, the United States delivered its first IVF baby, and the use of IVF has grown dramatically. IVF was a major breakthrough because it allowed for successful pregnancies in women that were previous deemed permanently infertile, such as when the fallopian tubes are both markedly damaged. IVF involves removal of eggs directly from the ovary, fertilization with sperm in the laboratory, followed by transfer of the embryos directly into the uterus, thereby bypassing the tubes. Although tubal disease was the original indication for IVF, many more indications have developed over the years. These include advancing maternal age, severe male factor infertility (whereby ICSI can be used to fertilize the egg), and endometriosis, amongst many others.
IVF is Generally Performed in the Following Manner:
The woman undergoes gonadotropin injections, which stimulate the ovaries to produce many eggs. Once the follicles (fluid filled sacs containing the eggs) reach a mature size, an HCG injection is administered which leads to final development and maturation of the eggs. Just before those eggs would otherwise be ovulated, they are retrieved under mild anesthesia in an operating room. This procedure is done by ultrasound guidance when the surgeon utilizes a narrow needle to retrieve eggs from the ovary through the vaginal wall. This sterile needle is attached to sterile suction tubing and a collecting vial. Once the fluid containing the eggs is removed from the follicles into the vials, they are handed to the embryologist who finds the eggs, places them in tiny droplets on a Petri dish, and then fertilizes the eggs using their partner’s or donor sperm. The sperm can either be mixed with the eggs to allow normal fertilization (conventional insemination) or by injecting one sperm into each mature egg (ICSI).
The fertilized eggs, now embryos, are allowed to grow and develop in culture media for typically 3 to 5 days. Then, generally one or two embryos, which have demonstrated appropriate development, are carefully and gently transferred into the uterine cavity. Embryos transfer is performed in the office under abdominal ultrasound guidance using a small, soft, sterile and flexible catheter. The embryos are placed within the tip of the transfer catheter and then injected within the uterine cavity once the catheter is placed through the cervical canal to the ideal spot within the uterus.
The pregnancy test is then performed 2 weeks after the egg retrieval. This process has revolutionized assisted reproductive technology and the way reproductive endocrinologists can help people in having a baby. Find an IVF Doctor | Free IVF Class | Class Testimonials
5) Third party reproduction: This is a general reference to a general process where another person provides sperm or eggs, or where another woman acts as a gestational surrogate, with the purpose of helping another person or couple have a child. The four types of third party reproduction are 1) sperm donation – a process by which donated sperm is used for insemination in the uterus, or for fertilization of eggs in the IVF process; 2) egg or ovum donation – a process by which an egg donor undergoes an IVF cycle in order to obtain her eggs which are then donated and fertilized. The resulting embryos are then transferred into the uterus of the future mother, known as the recipient. Usually no more than 1 – 2 embryos are transferred, and therefore additional embryos can be frozen, or cryopreserved, for future use; 3) embryo donation – a process where a fully developed embryo from another person in combination w/donor sperm, or couple who underwent IVF, are donated to another woman, the future intended mother, for transfer into her uterus; and 4) gestational surrogacy – a process where another woman will undergo an embryo transfer and carry the pregnancy for another person. Your physician will discuss these approaches to having a baby if appropriate to your particular case.
6) Surgery – After a thorough history, physical examination, and ultrasound are performed, your doctor may recommend surgery to correct and abnormality. In reproductive medicine, the most common surgical procedures are laparoscopy, hysteroscopy, and abdominal myomectomy (removal of uterine fibroids).
Laparoscopy is an operation performed in the abdomen or pelvis through small incisions, generally no more than a centimeter, with the assistance of a laparoscope attached to a camera which projects to a screen. It can either be used to inspect and diagnose certain conditions or to surgically correct an abnormality such as removing scar tissue, endometriosis, or a damaged fallopian tube. The procedure is performed in an outpatient setting in the vast majority of cases, and recovery time can be as little as a few days.
Hysteroscopy is the inspection of the uterine cavity through the cervix by a hysteroscope attached to a camera which projects to a screen. Through this technique, your physician can diagnose abnormalities such as fibroids or polyps within the uterine cavity, and via narrow instruments that run through the hysterosope, can remove or correct the great majority of these abnormalities. This procedure is performed in the outpatient setting. Recovery is generally no more than one day. Hysteroscopy can also be combined with laparoscopy when necessary.
Abdominal myomectomy is a surgical procedure performed through a very low horizontal abdominal incision allowing access to the uterus for removal of fibroids. This procedure can, in selected cases, also be performed laparoscopically, often with the assistance of a robot.
|Frequency||113 million (2015)|
Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects).
In humans, infertility is the inability to become pregnant/impregnate or carry a pregnancy to full term. There are many causes of infertility, including some that medical intervention can treat. Estimates from 1997 suggest that worldwide about five percent of all heterosexual couples have an unresolved problem with infertility. Many more couples, however, experience involuntary childlessness for at least one year: estimates range from 12% to 28%.”  20-30% of infertility cases are due to male infertility, 20-35% are due to female infertility, and 25-40% are due to combined problems in both parts. In 10-20% of cases, no cause is found. The most common cause of female infertility is ovulatory problems which generally manifest themselves by sparse or absent menstrual periods. Male infertilityis most commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.
Women who are fertile experience a natural period of fertility before and during ovulation, and they are naturally infertile for the rest of the menstrual cycle. Fertility awarenessmethods are used to discern when these changes occur by tracking changes in cervical mucus or basal body temperature.
World Health Organization
|“||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.||”|
One definition of infertility that is frequently used in the United States by reproductive endocrinologists, doctors who specialize in infertility, to consider a couple eligible for treatment is:
- a woman under 35 has not conceived after 12 months of contraceptive-free intercourse. Twelve months is the lower reference limit for Time to Pregnancy (TTP) by the World Health Organization.
- a woman over 35 has not conceived after 6 months of contraceptive-free sexual intercourse.
These time intervals would seem to be reversed; this is an area where public policy trumps science. The idea is that for women beyond age 35, every month counts and if made to wait another 6 months to prove the necessity of medical intervention, the problem could become worse. The corollary to this is that, by definition, failure to conceive in women under 35 isn’t regarded with the same urgency as it is in those over 35.
In the UK, previous NICE guidelines defined infertility as failure to conceive after regular unprotected sexual intercourse for 2 years in the absence of known reproductive pathology. 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.
Researchers commonly base demographic studies on infertility prevalence on a five-year period. Practical measurement problems, however, exist for any definition, because it is difficult to measure continuous exposure to the risk of pregnancy over a period of years.
Primary vs. secondary infertility
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. 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’.
Secondary 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 since their last live birth, during which they did not use any contraceptives.
Thus the distinguishing feature is whether or not the couple have ever had a pregnancy which led to a live birth.
The consequences of infertility are manifold and can include societal repercussions and personal suffering. Advances in assisted reproductive technologies, such as IVF, can offer hope to many couples where treatment is available, although barriers exist in terms of medical coverage and affordability. The medicalization of infertility has unwittingly led to a disregard for the emotional responses that couples experience, which include distress, loss of control, stigmatization, and a disruption in the developmental trajectory of adulthood.
Infertility may have psychological effects. Partners may become more anxious to conceive, increasing sexual dysfunction. 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. Emotional stress and marital difficulties are greater in couples where the infertility lies with the man.
Older people with adult children appear to live longer. Why this is the case is unclear and may dependent in part on those who have children adopting a healthier lifestyle, support from children, or the circumstances that led to not having children.
In many cultures, inability to conceive bears a stigma. In closed social groups, a degree of rejection (or a sense of being rejected by the couple) may cause considerable anxiety and disappointment. Some respond by actively avoiding the issue altogether; middle-class men are the most likely to respond in this way.
In the United States some treatments for infertility, including diagnostic tests, surgery and therapy for depression, can qualify one for Family and Medical Leave Act leave. It has been suggested that infertility be classified as a form of disability.
Antisperm antibodies (ASA) have been considered as infertility cause in around 10–30% of infertile couples. 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. 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.
Sexually transmitted infections
Infections with the following sexually transmitted pathogens have a negative effect on fertility: Chlamydia trachomatis and Neisseria gonorrhoeae. There is a consistent association of Mycoplasma genitalium infection and female reproductive tract syndromes. M. genitalium infection is associated with increased risk of infertility.
Mutations to NR5A1 gene encoding Steroidogenic Factor-1 (SF-1) have been found in a small subset of men with non-obstructive male factor infertility where the cause is unknown. Results of one study investigating a cohort of 315 men revealed changes within the hinge region of SF-1 and no rare allelic variants in fertile control men. Affected individuals displayed more severe forms of infertility such as azoospermia and severe oligozoospermia.
Factors that can cause male as well as female infertility are:
- DNA damage
- DNA damage reduces fertility in female ovocytes, as caused by smoking, other xenobiotic DNA damaging agents (such as radiation or chemotherapy) or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine
- DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage, smoking, other xenobiotic DNA damaging agents (such as drugs or chemotherapy) or other DNA damaging agents including reactive oxygen species, fever or high testicular temperature. The damaged DNA related to infertility manifests itself by the increased susceptibility to denaturation inducible by heat or acid  and/or by the presence of double-strand breaks that can be detected by the TUNEL assay.
- General factors
- Hypothalamic-pituitary factors
- Environmental factors
German scientists have reported that a virus called Adeno-associated virus might have a role in male infertility, though it is otherwise not harmful. Other diseases such as chlamydia, and gonorrhea can also cause infertility, due to internal scarring (fallopian tube obstruction).
The following causes of infertility may only be found in females. For a woman to conceive, certain things have to happen: vaginal intercourse must take place around the time when an egg is released from her ovary; the system that produces eggs has to be working at optimum levels; and her hormones must be balanced.
For women, problems with fertilisation arise mainly from either structural problems in the Fallopian tube or uterus or problems releasing eggs. Infertility may be caused by blockage of the Fallopian tube due to malformations, infections such as chlamydia and/or scar tissue. For example, endometriosis can cause infertility with the growth of endometrial tissue in the Fallopian tubes and/or around the ovaries. Endometriosis is usually more common in women in their mid-twenties and older, especially when postponed childbirth has taken place.
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 developed 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.
Sometimes it can be a combination of factors, and sometimes a clear cause is never established.
Common causes of infertility of females include:
- ovulation problems (e.g. polycystic ovarian syndrome, PCOS, the leading reason why women present to fertility clinics due to anovulatory infertility.)
- tubal blockage
- pelvic inflammatory disease caused by infections like tuberculosis
- age-related factors
- uterine problems
- previous tubal ligation
- advanced maternal age
- immune infertility
The main cause of male infertility is low semen quality. In men who have the necessary reproductive organs to procreate, infertility can be caused by low sperm count due to endocrine problems, drugs, radiation, or infection. There may be testicular malformations, hormone imbalance, or blockage of the man’s duct system. Although many of these can be treated through surgery or hormonal substitutions, some may be indefinite. Infertility associated with viable, but immotile sperm may be caused by primary ciliary dyskinesia. The sperm must provide the zygote with DNA, centrioles, and activation factor for the embryo to develop. A defect in any of these sperm structures may result in infertility that will not be detected by semen analysis. Antisperm antibodies cause immune infertility. Cystic fibrosis can lead to infertility in men.
In some cases, both the man and woman may be infertile or sub-fertile, and the couple’s infertility arises from the combination of these conditions. In other cases, the cause is suspected to be immunological or genetic; it may be that each partner is independently fertile but the couple cannot conceive together without assistance.
In the US, up to 20% of infertile couples have unexplained infertility. In these cases abnormalities are likely to be present but not detected by current methods. Possible problems could be that the egg is not released at the optimum time for fertilization, that it may not enter the fallopian tube, sperm may not be able to reach the egg, fertilization may fail to occur, transport of the zygote may be disturbed, or implantation fails. It is increasingly recognized that egg quality is of critical importance and women of advanced maternal age have eggs of reduced capacity for normal and successful fertilization. Also, polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility. However, a growing body of evidence suggests that epigenetic modifications in sperm may be partially responsible.
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.
Women over the age of 35 should see their physician or WHNP after six months as fertility tests can take some time to complete, and age may affect the treatment options that are open in that case.
A doctor or WHNP takes a medical history and gives a physical examination. They can also carry out some basic tests on both partners to see if there is an identifiable reason for not having achieved a pregnancy. If necessary, they refer patients to a fertility clinic or local hospital for more specialized tests. The results of these tests help determine the best fertility treatment.
Treatment depends on the cause of infertility, but may include counselling, fertility treatments, which include in vitro fertilization. According to ESHRE recommendations, couples with an estimated live birth rate of 40% or higher per year are encouraged to continue aiming for a spontaneous pregnancy. Treatment methods for infertility may be grouped as medical or complementary and alternative treatments. Some methods may be used in concert with other methods. Drugs used for both women and men include clomiphene citrate, human menopausal gonadotropin (hMG), follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) analogues, aromatase inhibitors, and metformin.
Medical treatment of infertility generally involves the use of fertility medication, medical device, surgery, or a combination of the following. If the sperm are of good quality and the mechanics of the woman’s reproductive structures are good (patent fallopian tubes, no adhesions or scarring), a course of ovarian stimulating medication maybe used. The physician or WHNP may also suggest using a conception cap cervical cap, which the patient uses at home by placing the sperm inside the cap and putting the conception device on the cervix, or intrauterine insemination (IUI), in which the doctor or WHNP introduces sperm into the uterus during ovulation, via a catheter. In these methods, fertilization occurs inside the body.
If conservative medical treatments fail to achieve a full term pregnancy, the physician or WHNP may suggest the patient undergo in vitro fertilization (IVF). IVF and related techniques (ICSI, ZIFT, GIFT) are called assisted reproductive technology (ART) techniques.
ART techniques generally start with stimulating the ovaries to increase egg production. After stimulation, the physician surgically extracts one or more eggs from the ovary, and unites them with sperm in a laboratory setting, with the intent of producing one or more embryos. Fertilization takes place outside the body, and the fertilized egg is reinserted into the woman’s reproductive tract, in a procedure called embryo transfer.
In vitro fertilization
IVF is the most commonly used ART. It has been proven useful in overcoming infertility conditions, such as blocked or damaged tubes, endometriosis, repeated IUI failure, unexplained infertility, poor ovarian reserve, poor or even nil sperm count.
Intracytoplasmic sperm injection
ICSI technique is used in case of poor semen quality, low sperm count or failed fertilization attempts during prior IVF cycles. This technique involves an injection of a single healthy sperm directly injected into mature egg. The fertilized embryo is then transferred to womb.
Fertility tourism is the practice of traveling to another country for fertility treatments. It may be regarded as a form of medical tourism. The main reasons for fertility tourism are legal regulation of the sought procedure in the home country, or lower price. In-vitro fertilization and donor insemination are major procedures involved.
Prevalence of infertility varies depending on the definition, i.e. on the time span involved in the failure to conceive.
- Infertility rates have increased by 4% since the 1980s, mostly from problems with fecundity due to an increase in age.
- Fertility problems affect one in seven couples in the UK. Most couples (about 84%) who have regular sexual intercourse (that is, every two to three days) and who do not use contraception get pregnant within a year. About 92 out of 100 couples who are trying to get pregnant do so within two years.
- Women become less fertile as they get older. For women aged 35, about 94% who have regular unprotected sexual intercourse get pregnant after three years of trying. For women aged 38, however, only about 77%. The effect of age upon men’s fertility is less clear.
- In people going forward for IVF in the UK, roughly half of fertility problems with a diagnosed cause are due to problems with the man, and about half due to problems with the woman. However, about one in five cases of infertility has no clear diagnosed cause.
- In Britain, male factor infertility accounts for 25% of infertile couples, while 25% remain unexplained. 50% are female causes with 25% being due to anovulation and 25% tubal problems/other.
- In Sweden, approximately 10% of couples wanting children are infertile. In approximately one third of these cases the man is the factor, in one third the woman is the factor, and in the remaining third the infertility is a product of factors on both parts.
Society and culture
Perhaps except for infertility in science fiction, films and other fiction depicting emotional struggles of assisted reproductive technology have had an upswing first in the latter part of the 2000s decade, although the techniques have been available for decades. Yet, the number of people that can relate to it by personal experience in one way or another is ever growing, and the variety of trials and struggles is huge.
Other individual examples are referred to individual subarticles of assisted reproductive technology
There are several ethical issues associated with infertility and its treatment.
- High-cost treatments are out of financial reach for some couples.
- Debate over whether health insurance companies (e.g. in the US) should be required to cover infertility treatment.
- Allocation of medical resources that could be used elsewhere
- The legal status of embryos fertilized in vitro and not transferred in vivo. (See also Beginning of pregnancy controversy).
- Pro-life opposition to the destruction of embryos not transferred in vivo.
- IVF and other fertility treatments have resulted in an increase in multiple births, provoking ethical analysis because of the link between multiple pregnancies, premature birth, and a host of health problems.
- Religious leaders’ opinions on fertility treatments; for example, the Roman Catholic Church views infertility as a calling to adopt or to use natural treatments (medication, surgery, and/or cycle charting) and members must reject assisted reproductive technologies.
- Infertility caused by DNA defects on the Y chromosome is passed on from father to son. If natural selection is the primary error correction mechanism that prevents random mutations on the Y chromosome, then fertility treatments for men with abnormal sperm (in particular ICSI) only defer the underlying problem to the next male generation.
Many countries have special frameworks for dealing with the ethical and social issues around fertility treatment.
- One of the best known is the HFEA – The UK’s regulator for fertility treatment and embryo research. This was set up on 1 August 1991 following a detailed commission of enquiry led by Mary Warnock in the 1980s
- A similar model to the HFEA has been adopted by the rest of the countries in the European Union. Each country has its own body or bodies responsible for the inspection and licensing of fertility treatment under the EU Tissues and Cells directive 
- Regulatory bodies are also found in Canada  and in the state of Victoria in Australia