Female Infertility Causes and Treatment 

Epidemiology Causes of female infertility Chromosome abnormalities Ovulatory disorders The oocyte factor Tubal infertility Endometriosis Implantation failure Recurrent miscarriage Lifestyle factors Psychological and occupational factors Diagnosis and management of anovulation Tubal disease Severe Endometriosis Superstimulation and intrauterine insemination ART Operative hysteroscopy Table: Causes of infertility in women

Normal fertility or fecundity has not been properly defined. A couple is said to have decreased fertility if they have not achieved pregnancy within 12 unprotected cycles. However, this definition is arbitrary. Very fertile couples achieve pregnancy within the first few cycles, and others make it just within 12 cycles. There may, in fact, be important biological differences between couples who achieve pregnancy in one or two months and those who succeed only after 12 or more cycles.

In taking a history, two elements are essential--the age of the woman and the duration of infertility. Fecundity in women decreases after the age of 30 years, and infertility accelerates after 35 years. These observations are supported by the demonstration that the pregnancy rate per single embryo transfer with natural cycle in-vitro fertilisation (IVF) is 17% for women younger than 30, 13% for those aged 31-35, and 11% for those aged 36-40. Duration of infertility is another important variable in determining the chance of pregnancy. For example, analysis of the cumulative pregnancy rates in couples with male-factor problems, and a short duration of infertility, indicates that substantial spontaneous pregnancy rates still occur.

Epidemiology

Most studies from industrially developed countries indicate that about 15% of all couples will experience either primary or secondary infertility at some time during their reproductive lives, and about half these couples will never succeed in having as many children as they wish. Most epidemiological reports on fertility centre on the USA and western Europe. Our knowledge on fecundity in the industrially less-developed countries is limited.

Little is known about secular trends in the prevalence of infertility. Although some infectious causes such as tuberculosis and gonorrhoea are less common now, infertility due to chlamydia infections and environmental pollution may be increasing. Inconsistency in epidemiological studies makes it virtually impossible to offer firm conclusions about the trend in infertility rates. On the other hand, the numbers of patients attending fertility clinics are now so high that it may indeed reflect a growing problem. In 1990, women were 2-3 years older when they delivered their first child than in 1970; significantly more women never had a child. 17% of Danish women employed in the financial sector had no children at the age of 35. Whether this changing trend in fertility is due to social or biological factors remains to be seen.

Causes of female infertility

The causes of infertility may very from one geographic and social area to another. A WHO task force revealed the following causes of infertility in women: tubal factor 36%, ovulatory disorders 33%, endometriosis 6%, and no demonstrable cause 40%. A similar distribution was found in Asia, Latin America, and the Middle East, whereas in Africa most infertile women had tubal infertility. Unexplained infertility (both partners considered) has been found in 8 to 28% of couples.

Rather than reviewing all known causes, we shall focus on some common causes of female infertility and also emphasise new developments. Male infertility has been addressed in a companion article, in which sperm-oocyte fusion, unexplained infertility, and untreatable infertility have been discussed.

Chromosome abnormalities

Chromosome abnormalities may cause infertility in both men and women, although they are most common among men. Sex chromosome abnormalities in the phenotypic female include variants of gonadal dysgenesis (including Turner's syndrome) and androgen insensitivity, but these patients rarely attend fertility clinics. In contrast to patients with androgen insensitivity syndrome, women with gonadal dysgenesis usually have a preserved uterus. Thus, they may achieve pregnancy by egg donation and IVF.

Ovulatory disorders

Hypothalamic and hyperprolactinaemic anovulation are caused by an abnormal pulsatile release of gonadotropin releasing hormone (GnRH)--probably due to altered endorphinergic or dopaminergic tone. Hypothalamic anovulation is often reversible when mediated by exogenous factors such as stress of weight loss.

Premature ovarian failure may be genetically determined or associated with autoimmune disease. In the resistant ovarian syndrome, primordial follicles are present but fail to mature owing to lack of sensitivity to follicle-stimulating hormone (FSH). Luteinising hormone (LH) receptor antibodies, not linked to presence of an autoimmune disease, may also be a cause of ovarian failure.

Polycystic ovarian disease is thought to be the commonest cause of anovulatory infertility. Besides anovulatory disturbances, the condition is associated with hirsutism, obesity, and endometrial carcinoma. The early miscarriage rate after induction of ovulation is also increased. Weight loss is often followed by the return of ovulatory cycles.

Research based on serial hormone measurements and ultrasonography has given us new knowledge on the normal and abnormal menstrual cycle. A conception cycle is characterised by a preovulatory follicle with a diameter of at least 18 mm, follicle reduction to less than 50% of its size at ovulation, and serum progesterone above 25 nmol/L in the luteal phase. Many abnormal cycles previously classified as being due to a luteal insufficiency may be a result of anovulation due to failure of the follicle to rupture. Such events can be classified as a "cyst" cycle. Other cycle aberrations include luteinised unruptured follicle, the empty follicle, and ovum retention (or entrapment). The clinical significance of such abnormal cycles as causes of infertility remains to be elucidated.

The oocyte factor

Deterioration of oocyte quality causing a lower pregnancy rate and an increased abortion rate may be responsible for considerable age-related decrease in female fecundity, Thus, there is a 50% decrease in female fecundity from age 25 to 35. It is of interest that the decrease in fecundity does not seem to be due to recognisable ovulatory disturbances in older women, and egg donation to women above 40 years of age is associated with a normal conception rate. Kola and colleagues have emphasised that this decrease in female fecundity is often due to chromosomal abnormalities in human eggs. Aneuploidy occurs in about 26% of human oocytes but in only 10% of human spermatozoa. This high rate of abnormality is apparently due to precocious division of chromosome univalents at anaphase I of meiosis; this causes trisomy and becomes more frequent with increasing maternal age.

A new hypothesis is that hypersecretion of LH during the mid and late follicular phase of the cycle is responsible for the impairment of fertilisation of the oocytes and increased early pregnancy loss. Experience from IVF treatments indicates that high LH concentrations during the late follicular phase are associated with lower rates of fertilisation, cleavage, and pregnancy. Furthermore, oocytes are more fragmented and show asymmetry of blastomere size, indicating that the oocyte might be in the early stage of atresia when fertilised. These findings were supported by an observation of a significantly higher conception rate after 2 years of follow-up among 147 women who had normal mid follicular serum LH than did a group of 46 women with high LH concentrations (88% vs 67%) and lower frequency of miscarriage (12 % vs 65%).

The precise effect of raised LH is not known; oocytes seem to lack LH receptors, Some investigators find that patient age and low serum oestradiol are better than serum LH for predicting miscarriage in women with polycystic ovarian disease. It has been speculated that high LH concentrations cause premature cumulus expansion followed by disruption of intercellular coupling and untimely initiation of meiosis. The final result of this ill-timed but otherwise normal sequence of events would be ovulation of physiologically "aged" oocytes. Animal and human data suggest that delayed fertilisation is associated with poor fertilisation and increased early pregnancy loss.

Patients with polycystic ovarian disease tend to have raised LH concentrations as do those with polycystic ovaries and preserved ovulatory cycles. About 20-25% of normally menstruating women have polycystic ovaries. Thus, it is possible that some apparently normal women with normal ovulatory cycles have polycystic ovaries, and consequently a low fecundity due to a decreased fertilisation rate and an increased risk of pregnancy wastage.

Tubal infertility

A history of salpingitis is associated with the highest relative risk of infertility. Pelvic inflammatory disease (PID) due to sexually transmitted microorganisms, such as gonococci, chlamydia, or other pathogens, is the main cause of tubal infertility. In addition, PID is associated with a 2 to 8-fold risk of subsequent ectopic pregnancy. Follow-up studies on fertility of women with laparoscopically documented PID have shown that for each episode of infection there is at least a 10% risk of subsequent tubal infertility, irrespective of the type of microorganism causing infection. The effect seems to be additive, with risk of tubal infertility doubling after a second episode of PID.

Chlamydia is the most common cause of tubal infertility; 3 out of 4 women with tubal infertility will be seropositive for chlamydia compared with 1 out of 4 fertile women. Work on laboratory animals has thrown some light on the mechanisms behind PID-induced tubal damage. After a single inoculation of chlamydia in the ovarian tubes of monkeys, there is negligible or no damage. Serial inoculations, however, cause alterations in the tubal mucosa, intratubular adhesions, and distal obstruction; this may represent an immune-mediated destruction or exacerbation of chronic infection.

Tubal infertility may also follow septic abortion, puerperal infection, suppurative appendicitis, peritonitis of other causes, or abdominal surgery. Infertility caused by some of these conditions is partly preventable; uncomplicated appendicectomy does not increase the risk of subsequent tubal blockade, whereas a ruptured appendix causes a 5-fold increase in such risk.

Endometriosis

The cause of endometriosis is unknown. The diagnosis is frequently made because of the technical ease of modern videolaparoscopy. The glib explanation is that endometriosis follows retrograde menstruation, but much laboratory and clinical evidence suggests that endometriosis is more complex than this. We have recently suggested that endometriosis is a disease of angiogenesis since in endometriosis, the endometrium, as well as endometriotic plaques, seems to have greater angiogenic activity than does the endometrium of normal women.

Severe endometriosis can compromise fertility by causing pelvic adhesions, distorted anatomy, and ovarian or tubal damage. In addition, the ovulatory process and ovum capture may be disturbed. The relation between minimal endometriosis and infertility is based on indirect evidence, such as the higher fecundity of infertile women requiring donor insemination without visible endometriosis than women with endometriosis. This association is less clear than earlier believed. Firstly, the apparently high frequency ( 20-40%) in infertile women compared with fertile controls (< 10%) may be due to observer and reporting bias. Secondly, neither medical nor surgical treatment of the endometriotic foci increases the pregnancy rate. Thirdly, there are conflicting data about the monthly fecundity of women with minimal or mild endometriosis. Controlled studies have not shown any treatment-dependent improvement in fertility with medical suppression of endometriosis or surgical excision and ablation. This includes the newer endoscopic operative laparoscopy approaches. Therefore, the laparascopic diagnosis of minimal or mild endometriosis does not necessarily mean that the cause of the infertility has been found.

Implantation failure

Little is known about the role of implantation failure as a cause of infertility. The traditional concept is that in some women insufficient secretion of progesterone will cause an endometrium that is non-receptive. The uterine receptivity for nidation of the blastocyst is thus impaired, resulting either in lack of nidation or in early pregnancy loss. This notion has been seriously questioned. Firstly, the endometrial histology may not reveal a valid "bioassay" of progesterone secretion. Secondly, "luteal insufficiency" may occur as often in fertile as in infertile women, and there is no association between this condition and the fecundity of the couple. Thirdly, deficient progesterone secretion may primarily reflect ovulatory disturbances.

Endometrial receptivity, nidation, and early blastocyst development are crucial. As much as 10% of early implantations occur without clinical evidence of pregnancy; this can be due either to defective implantation or to blastocyst defects. The endometrial structure, as assessed by transvaginal ultrasonography, is of some value in predicting the chance of pregnancy and of early pregnancy loss. A thick, triple-layered endometrium with normal echogenicity predicts a favourable outcome.

Recent work has shown that the secretion of an oligosaccharide epitope produced by the endometrial glands during the peri-implantation phase and glycoproteins serving as adhesion molecules may be markers of disturbed endometrial receptivity. Thus, new developments in assessment of endometrial receptivity are promising and may lead to diagnosis of specific endometrial defects causing infertility.

Recurrent miscarriage

One-third of women with repeated pregnancy wastage also have subfertility, defined as delays in conception of more than 12 months. Recurrent abortion is associated with parental chromosome abnormalities, antiphospholipid antibodies, and uterine cavity abnormalities. Perhaps the single most important cause was polycystic ovaries, which was found in 46% of 500 cases. 60% of women with polycystic ovaries had evidence of abnormal LH secretion. Thus, although two-thirds of women with recurrent abortions have no difficulty in achieving pregnancy there is little doubt that there is a link between repeated abortion and infertility.

Lifestyle factors

As in men several lifestyle factors may have consequences for reproduction, including habits of diet, clothing, exercise, and the use of alcohol, tobacco, and recreational drugs (eg, marijuana). Little is known about these lifestyle factors apart from tobacco smoking in women. There is evidence of an increased risk of infertility and delayed conception rate among women who smoke.[ 20] Furthermore, the eggs of smokers have decreased IVF capacity.

Psychological and occupational factors

Being infertile may generate psychological disturbances. However, do psychological factors actually have a causal or contributory role in some cases of infertility? One myth about infertility is that adoption increases the couple's fertility. This is not so. Several studies have used psychological testing of large populations of infertile women compared with controls. However, no consistent differences in psychological variables, such as anxiety, depression, and social adjustment, were found.

There might be an association between stress and infertility among women with ovulatory disorders or unexplained infertility, but the precise role of stress is uncertain. This does not mean that stress cannot cause infertility. Hypothalamic amenorrhoea, for instance, can be induced by stressful life events, and anorexia nervosa is clearly a psychogenic condition.

Most occupational studies have examined male reproductive function, usually by measuring semen characteristics. Refinement of epidemiological research methods has enhanced the possibility of detection of environmental hazards to female fecundity. A recent example is the reporting of delayed conception in dental assistants with high exposure to nitrous oxide. In women, occupational exposure to textile dyes, lead, mercury, and cadmium has been associated with infertility. The associations were mostly found in women classified as having unexplained infertility. In fertile women, the same exposures have been associated with delayed conceptions. Environmental, nutritional, and socioeconomic factors have been discussed.

Diagnosis and management of anovulation

Regular menstrual cycles ( 21-35 days), ovulatory mid-cycle pain, and clear cervical mucus suggest ovulation. In women with irregular cycles, repeated progesterone measurements may be necessary to identify anovulation. Decreased gonadotropin secretion associated with low or absent GnRH secretion, weight loss leading to bodyweights of less than 47 kg, or a body mass index below 19, frequently lead to anovulation. However, in many women, chronic anovulation associated with oligomenorrhea occurs often in association with normal. serum FSH, LH, and prolactin levels. Serum prolactin may be raised with secondary amenorrhoea and galactorrhoea. In such cases, increased serum prolactin may be associated with a microprolactinoma on computed tomographic scanning in 80% of women. High serum prolactin can be associated with hypothyroidism, and measurements of free thyroxine index and thyroid-stimulating hormone are helpful.

The polycystic ovary is best diagnosed on vaginal ultrasonic examination by finding an enlarged ovary with eight or more follicles greater than 6 mm in diameter, accompanied by an ectogenic stroma. When this ovarian ultrasound finding is associated with infertility, the clinical term used to describe this disorder is polycystic ovarian syndrome. This syndrome! can be accompanied by chronic anovulation, oligomenorrhea, or amenorrhoea, and can occur with normal concentrations of serum FSH, and LH:FSH ratio greater than 3.

Management of anovulation is designed to enable the couple to have one healthy baby at a time. Because some therapeutic agents used in ovulation induction are hazardous and expensive, attention to simple issues such as weight disorders (body mass index < 19 or >25) are important as the first approach to management. Empirical therapy with agents such as clomiphene citrate without documentation of anovulation should not be given, and any form of ovulation induction should be monitored for effectiveness--eg, estimations of mid-luteal phase progesterone.

If hyperprolactinaemia is present, treatment with the ergot derivative bromocriptine, a D2 dopamine agonist, usually results in normal prolactin levels within 4 weeks. Anovulation associated with polycystic ovarian syndrome should be treated with clomiphene citrate. A regimen of 50 mg per day (days 5-9 of the cycle) is typical although the condition responds to a regimen of 25 mg daily (days 2-6). If ovulation, as indicated by serum progesterone greater than 30 nmol/L, is not achieved, the clomiphene citrate dose is increased in the next cycle until a maximum daily dose of 150 mg is achieved.

Failure to respond to clomiphene or bromocriptine should necessitate referral to specialist units since subsequent treatment with GnRH or gonadotropins requires careful monitoring and experience owing to the risk of multiple pregnancies and ovarian hyperstimulation syndrome. Even a twin pregnancy increases not only fetal risks of spontaneous abortion, malformation, preterm birth, and perinatal outcome, but also maternal risks of morbidity and death. For some women multiple pregnancy reduction is an option.

GnRH therapy is the treatment of choice for hypogonadotropic hypogonadism since these women are GnRH deficient. Subcutaneous GnRH, 5-20 mug every 90 rain, has produced a normal cumulative conception rate in our patients. Intravenous GnRH is equally effective and both regimens are associated with a lower frequency of multiple pregnancy and ovarian hyperstimulation syndrome than gonadotropin therapy. Disadvantages include cost and inconvenience of the delivery apparatus and the risk of endocarditis with intravenous GnRH administration.

Gonadotropin treatment with low-dose human menopausal gonadotropin, or recombinant human FSH, and human chorionic gonadotropin should be used if clomiphene citrate fails to induce ovulation. Careful monitoring of ovarian responsiveness with ultrasound screening and serum oestradiol measurements to assess follicular growth are aimed at achieving ovulation of a single follicle and avoidance of ovarian hyperstimulation, which can occur more readily in polycystic ovarian syndrome. Failure to achieve conception after ovulatory cycles should suggest the need for assisted reproduction, such as IVF or gamete intrafallopian transfer (GIFT).

Ovulation induction over 20 years in a tertiary referral unit resulted in a multiple pregnancy rate of 13%, including a 3% triplet rate. Over 2 years to December, 1990, we treated 71 patients and achieved an ovulation rate of 76% with no evidence of an influence of body mass index on outcome. No differences in outcome were noted with women who had polycystic ovarian syndrome and other forms of clomiphene-resistant anovulation; cumulative pregnancy rates after 9 cycles were 81.2% and 80.6%, respectively.

Tubal disease

With the increasing success and availability of assisted reproduction techniques (ART), there is considerable controversy about the place of microsurgery. Specialised units should achieve fecundity rates of 15-25% per cycle to match ART. Proximal tubal obstruction or endometriosis represent the greatest challenge.

Salpingo-ovariolysis is the procedure to remove adhesions from the uterine tubes and ovaries. Equivalent intrauterine pregnancy rates have been reported after salpingo-ovariolysis via laparotomy or operative video-laparoscopy. In the largest report of 92 subjects with moderate to severe adnexal adhesions, 46% of all intrauterine pregnancies occurred within 6 months. This fecundity rate must be compared with that available in ART units.

Fimbrioplasty removes the fimabrial adhesions and attempts to repair fimbrial disease. Microsurgical fimbrioplasty by laparotomy or laparoscopic video-fimbrioplasty has shown equivalent intrauterine pregnancy rates. In both procedures, the ectopic pregnancy rate is about 5%. Salpingoneostomy, which aims to establish a new uterine tubal orifice as an alternative to ART, may be done by laparotomy or laparoscopy, but most series are small, the fecundity rates are often not given, and not many centres have much experience of this operation. Certainly, laparoscopic salpingoneostomy should be attempted only by experienced endoscopic surgeons.

Falloposcopy is a method of transcervical uterine tubal cannulation. After the success of GIFT for ART in the 1980s, cathetefisation of the uterine tube from the vagina for retrograde GIFT procedures was reported. High resolution vaginal ultrasonography combined with catheter technology from angiography (modified for cannulation of the uterine tube) advanced this infertility treatment. In addition to ultrasound imaging, fluoroscopic imaging and even no imaging in the manoeuvre of tactile tubal cannulation were undertaken for retrograde GIFT procedures. In balloon tuboplasty, a balloon rather than wire is used to apply lateral stretch to the walls of the uterine tubes; this may help breakdown adhesions and strictures in the uterine tube. One multicentre study of the treatment of bilateral proximal tubat occlusion has been reported. Early series indicate pregnancy rates between 23 and 39% over 6 months, with 6-month tubal patency rates between 35 and 82%. Falloposcopy has potential not only for ART but also for tubal sterilisation and the diagnosis and treatment of ectopic pregnancy.

Severe Endometriosis

The treatment of choice for moderate or severe endometriosis associated with mechanical damage is surgery. The role of medical treatment is still unclear owing to lack of details of infertility status and of characteristics such as age of the patient and duration of infertility in reports of medical treatment.

In view of the current uncertainty of the relation between mild endometriosis and infertility, it would seem reasonable in young patients to adopt. expectant management for 6-12 months after laparoscopy, when 20% of patients will conceive. Repeat laparoscopy is indicated for those not pregnant after 6-12 months, surgery and/or medical therapy for those in whom endometriosis has progressed, and further expectant management or GIFT for women in whom the endometriosis has improved or remained static. In older patients, we recommend GIFT.

The success of ART, mainly IVF, in patients with endometriosis has been controversial. Recent studies found similar fertilisation and cleavage rates, embryo morphology and quality, and oestradiol responses and drug requirements for ovulation induction among women with and without endometriosis. However, all reported reduced follicle and oocyte numbers with ultrasound-guided vaginal ovum pickup. The data on pregnancy rates are less consistent, with reports of no reduction in pregnancy rates or significantly reduced pregnancy rates in women with stage III and IV endometriosis and an increase in early spontaneous abortion.

Superstimulation and intrauterine insemination

Superstimulation in ovulatory women by use of gonadotropins in addition to intrauterine insemination with male-partner semen is increasingly used in couples with unexplained infertility, mild endometriosis, and combined male and female factors. The aim is to increase the number of gametes (both male and female) at the fertilisation site. Published series are of small numbers of couples. The cycle fecundity is around 10-15% per cycle. The appeal of this technique is that it seems simple. The main concern is that when gonadotropins are used, the multiple pregnancy rate may be as high as 30-40%, and extreme multiple pregnancies (sextuplets or higher) have appeared. Data with single, normal babies as the endpoint are awaited.

ART (assisted reproduction techniques)

The treatment of uterine tubal disease, unexplained infertility, and continuing infertility in the couple with previous anovulation has been revolutionised by ART. Observations accumulated from various centres over several years of ART on a large number of couples show a significantly improved fecundity of 15-25% per cycle. Endpoints such as pregnancy rates per ART cycle attempted, clinical pregnancy rates per embryo transfer, and births per cycle attempted show that ART increases substantially the fecundity of the infertile couple when simpler treatments have been unsuccessful. It is important, however, to emphasise that these techniques are expensive, stressful, and in some instances, hazardous and should therefore not be used without adequate investigations and trials of alternative therapeutic approaches.

Advances in ART have helped infertile couples in which the male partner has very few spermatozoa or spermatozoa that do not fertilise. Microdrop insemination, subzonal insemination, and intracytoplasmic sperm injection have been milestones in ART. In intracytoplasmic sperm injection, a single sperm is injected directly into the cytoplasm of the oocyte. Reproductive medicine has advanced to the extent that only 1 spermatozoan needs to be available for fertilisation by intracytoplasmic sperm injection compared with 10 during sexual intercourse. Van Steirteghem and associates have reported over 200 births after intracytoplasmic sperm injection. Fertilisation rates of 55% were observed in these series. Patients included men with less than 4% normal spermatozoa, with less than 10 spermatozoa in the whole ejaculate, and even patients with no motile sperm. Pregnancy rates were 22% per ART cycle commenced and 29% per ART cycle reaching embryo transfer. Pregnancy loss occurred in 26%,

For women with primary ovarian failure, ART offers the prospect of conception with oocyte donation associated with cyclic hormonal replacement therapy to prepare the endometrium.

Pregnancies associated with ART have an increased pregnancy wastage partly related to an increased multiple pregnancy rate. In some instances ovarian hyperstimulation syndrome may complicate ovulation induction. Two studies have reported an increased risk of ovarian cancer in women receiving ovulatory stimulants. However, the small numbers of patients, wide confidence intervals, and lack of important information, such as cause of the woman's infertility, types of drugs and doses used, and histology of the ovarian tumours, have led to doubt about the conclusions.

Operative hysteroscopy

Advances in operative hysteroscopy make this the procedure of choice for a septate uterus in a patient with recurrent pregnancy loss in whom all other factors have been excluded. All other co-existing factors should be treated to decrease the miscarriage rate before undertaking uterine surgery in such patients. Hysteroscopic metroplasty in patients with recurrent pregnancy loss should allow approximately 75% of patients to give birth at term. There is no benefit from inserting an intrauterine device at the end of hysteroscopic metroplasty to separate the uterine walls after surgery. Repeat diagnostic hysteroscopy or a hysterosalpingogram can be undertaken 3 months after hysteroscopic metroplasty to assess the uterine contour and proximal tubal ostia. After hysteroscopic metroplasty, pregnancy can be attempted without a lengthy waiting period as in the earlier operation of abdominal metroplasty. Moreover, there is no need for a subsequent caesarean section.

Panel: Generally accepted definitions of infertility and infecundity

Information is presented in the following order: Term; definition; clinical definition; subdivision

Infertility; Inability of couple to obtain clinically recognisable pregnancy, to achieve fertilisation of gametes; Couple does not achieve clinically/biochemically (hCG) recognisable pregnancy after 12 mo of intercourse; Resolved infertility/infecundity (subfertility/subfecundity): episode that is sooner or later followed by conception/birth. Unresolved infertility/infecundity: episode that is not followed by conception/birth

Infecundity Inability of couple to achieve livebirth; No pregnancy resulting in livebirth after 12 mo of unprotected intercourse

* May be primary or secondary, depending on whether the couple has ever achieved pregnancy/livebirth.

Table: Causes of infertility in women

Mechanism                         Condition

Absent gonadal tissue          Turner's syndrome and variants
                                        Pure gonadal dysgenesis
                                        Bilateral ovariectomy
Impaired gamete production   Hypogonadotropic hypogonadism
and function                       Hypothalamic anovulation
                                       Hyperprolactinaemic anovulation
                                       Complete androgen insensitivity
                                       Polycystic ovarian syndrome
                                       Premature ovarian failure
                                       Resistant ovarian syndrome
                                       Cyst cycles
                                       Luteinised unruptured follicle
                                       Ovum retention
                                       Oocyte factor ("aged" oocyte)
                                       Cytotoxic drugs (cydophosphamide)
                                       and other alkylating drugs
                                       Other drugs (dopamine antagonists,
                                       anti-inflammatories, anabolic
                                       steroids)
                                       Irradiation
                                       Smoking?
Impaired gamete transport    Malfunction of ovum capture and
                                       cilia mediated transport
                                       Tubal infertility
                                       Endometriosis
                                       Cervical factor
                                       Antisperm antibodies
Impaired conception            Polycystic ovaries
                                       Smoking
                                       Abnormalities in sperm adhesion
                                       molecules ZP2 and ZP3
Recurrent miscarriage          Chromosomal aberrations
                                       Oocyte factor
                                       Coagulation disturbances
                                       Polycystic ovaries
                                       Gross uterine anomalies

Stimulating Ovulation A problem with ovulation is one of the common-est causes of infertility and is probably the most successful to treat....

Last updated Jan 4/07