The most commonly accepted definition of the term "infertility' is the inability of a couple to achieve pregnancy (regardless of cause) after one year of regular unprotected sexual intercourse. It may be primary where no conception has ever taken place before or secondary where it has irrespective of the outcome.

Prevalence

Infertility is a worldwide problem. It affects approximately 15% of couples of reproductive age.

Its prevalence has been stable during the past three decades, although a shift in aetiology and in the age of the patient population has occurred.

In developed countries, where family planning and professional career development are practiced, some women postpone childbearing until after age 30-40 years. Fertility is maximal between the ages of 18- 26 and declines after the age of 35.

The reproduction process requires the interaction and integrity of the female and male reproductive tracts, which allows for the release of a normal preovulatory oocyte (egg), the production of adequate spermatozoa, the normal transport of the gametes to the ampullary portion of the fallopian tubes (where fertilization usually occurs), and the subsequent transport of the embryo up to the endometrial cavity for its normal implantation and further development.

The origin of infertility is similarly due to male or female factors; the causes are multiple. Female factors account for 45% of infertility. Male factors account for 20% of infertility. Male and female factors combined are attributed to cause 20% of infertility. The aetiology is unknown in 11% and can also be categorized as a normal infertile couple (NIC), indicating that all findings from standard tests used to evaluate the couples are normal. In NICs, the actual cause for infertility cannot be detected by conventional methods because it may be at the oocyte/sperm level or it may be due to the quality of the embryo or to any disruption at the implantation site level. Thankfully, this are few in minority. Other causes such as inadequate exposure to sexual intercourse, e.t.c are identified in 4%.

Secondary factors have been associated with an increased risk of infertility. Examples include environmental and occupational factors; toxic effects related to tobacco, marijuana and other drugs; exercise; malnutrition; advanced age; pelvic inflammatory disease (PID); endometriosis.

Environmental and occupational factors

There is rising concern regarding the impact of environmental factors on infertility.Excessive radiation damages the germinal cells (part where spermatozoa are produced) of the testes. Exposure to lead or other heavy metals and pesticides have also been associated with male infertility.

Toxic effects related to tobacco, marijuana, alcohol and other drugs

Smoking has been associated with infertility in both males and females. In experimental animals, nicotine and polycyclic aromatic hydrocarbons block spermatogenesis and decrease testicular size. In women, tobacco alters the cervical mucus and the cilial (surface) epithelium and affects gamete transport.

Marijuana and its metabolite, delta-9-tetrahydrocannabinol, inhibit the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) essential reproductive hormones, thus causing ovulatory disorders in women. Marijuana use affects males by decreasing quantity and the quality of the sperm.

In women, the effects of alcohol are related more to severe consequences for the foetus. Nevertheless, chronic alcoholism is related to ovulatory disorders and, therefore, interferes with fertility. Alcohol use by males interferes with the synthesis of testosterone and has an impact on sperm concentration. Alcoholism may delay the sexual response and may be contributory to erectile dysfunction (impotence).

Exercise

Exercise should be encouraged as part of normal activities. However, when done in excess is deleterious, especially for long-distance runners. Jogging stimulates the secretion of endorphins, and excessive secretion of endorphins interferes with the normal production of FSH and LH, in turn inducing ovulatory disorders. In males, excessive exercise has been associated with low sperm count(oligospermia).

Malnutrition

Obesity has an impact on infertility only when the female patient's weight reaches extremes. Although weight loss associated with anorexia nervosa or bulimia induces hypothalamic amenorrhea, a low FSH level, and low LH secretion, weight gain is tolerated better.

Advanced age

The prevalence of infertility rises dramatically as age increases . Age affects female fertility dramatically, but males are not affected as much; anecdotal reports exist of men fathering children when older than 80 years. Testosterone levels decrease, gonadotropin levels increase, sperm concentration and semen volume change, and libido decreases. In addition, the incidence of birth defects increases.

Pelvic inflammatory disease

PID has been associated with gonorrhea and chlamydia infection. The rate of damage to the fallopian tubes increases with subsequent PID episodes. PID can be diagnosed clinically and confirmed by results from cervical culture and serologic antibody assays for gonorrhea and chlamydia. In some cases, a patient never recalls having had an acute PID episode; however, years later, the incidental finding of tubal obstruction after hysterosalpingogram (HSG) or laparoscopy may be the only indication of previous PID.

Endometriosis

Endometriosis remains an enigmatic disease state that affects women during their reproductive years. It is the presence of actively functioning endometrial tissue in any place other than the endometrial cavity of the uterus. The incidence is commoner in higher socioeconomic class who tend to defer pregnancy. It is also commoner in the Caucasian than Blacks. The course of the disease is unpredictable. Infertility and pelvic pain are the 2 major complaints of patients with endometriosis.

Minimal and mild endometriosis is hypothesized to reduce fertility by immunological mechanisms. Severe endometriosis with damage to the fallopian tubes and ovaries due to adhesions or the presence of endometriomas is an obvious cause of infertility.

Endometriosis has been associated with ovulatory disorders.

Management

Infertility is a problem that involves both partners equally. The consultation is incomplete if only either the man or woman is evaluated. Anxiety is very common, and many couples seek consultation after a few months of unprotected intercourse. Diagnostic testing is unnecessary if the couple has not attempted to conceive for at least 1 year, unless they have a history of a male factor, endometriosis, a tubal factor, PID, or pelvic surgery. A brief explanation of the physiology of reproduction and reassurance are enough to lessen the anxiety of the couple.

History

General medical questioning will reveal a history regarding the type of infertility (primary or secondary) and its duration. The couple would provide information on issues of frequency of intercourse, use of lubricants , use of vaginal douches after intercourse, , a history of previous pregnancies and their outcomes; history of previous infertility evaluation and treatment A history of present and previous medical records,at the initial consultation. other questions asked should query for a history of sexually transmitted diseases (STDs); surgical contraception (eg, vasectomy, tubal ligation); lifestyle methods vis -a-vis consumption of alcohol, tobacco, and recreational drugs (amount and frequency); occupation; and physical activities.

Specific questioning of the female should elucidate about their menstrual history, frequency, and patterns since menarche. A history of visual disturbances, breast discharge,weight changes, hirsutism, frontal balding, anterior neck sweeling, abdominal swelling and acne should also be addressed. A history of the use of contraceptive is also sought.

Male patients provide information about previous SFA results, history of impotence, premature ejaculation, change in libido, history of testicular trauma, groin surgery, previous relationships, history of any previous pregnancy, and the existence of offspring from previous partners.

Physical

A physical examination should be completed. Routine records of blood pressure, pulse rate, and temperature (if applicable) are needed.

Measure height and weight to calculate the body mass index, and measure arm span when indicated. The body is generally examined for signs that could point to an underlying medical condition or structural abnormality that are known to cause infertility.

For the female, a thorough pelvic examination establish the direction of the cervix, the size and position of the uterus and any lesions that could indicate the existence of venereal disease.

The male partner is examined with particular attention being given to congenital abnormalities of the genital tract (eg, hypospadias, cryptorchid, congenital absence of the vas deferens). Testicular size, urethral stenosis, and presence of varicocele are also determined. A groin scar from previous inguinal hernia repair can indicate an accidental ligation of the spermatic artery or vas deferans.

Evaluation of infertile couples should be organized and thorough. The findings must be discussed with the couple after completion of the history and physical examination.

Evaluation of the male partner
The male partner must submit a semen sample for a comprehensive semen analysis.

The semen sample should preferably be collected at the laboratory that will conduct the test, however, if the sample must be collected at home, it must be collected in a sterile plastic container and delivered to the laboratory at body temperature not later than 30 minutes after ejaculation.

Some patients cannot produce a semen sample through masturbation. Therefore, the sample can be collected through intercourse, using a special nonspermicidal condom.

To optimize results, the semen sample should be collected after a period of 3 days but no more than 5 days of sexual abstinence.

Seminal Fluid Analysis

The basic semen analysis assesses the characteristics of sperm concentration, motility, morphology, and viability. The guideline values are stated below:

Volume - 2-5 mL

pH - 7.2-7.8

Sperm concentration - 20 million or greater

Motility - 50%, forward progression

Morphology - Normal sperm (50% or greater)

White blood cells - Less than 1 million cells/mL

Specific biochemistry analyses relevant to the accessory sex gland functions can be performed using the semen sample. These include fructose from the seminal vesicles, zinc and acid phosphatase from the prostate gland, and alpha-glucosidases and carnitine from the epididymis.

Sperm agglutination indirectly indicates the presence of sperm antibodies. The immunobead test can be performed either directly on the sperm or indirectly on the sperm and blood.. Sperm antibodies are associated with infection (ie, orchitis), testicular trauma, and a history of vasectomy.

Interpretation of semen analysis

Spermatogenesis takes approximately 72 days. Abnormal semen analysis results can be attributed to various unknown reasons (eg, short period of sexual abstinence, incomplete collection, poor sexual stimulus); therefore, repeating the semen analysis at least 1 month later is important before a diagnosis is made. Explaining to the patient the normal fluctuation that can occur between semen samples is also important.

Azoospermia indicates absence of sperm that could be related to congenital absence or bilateral obstruction of the vas deferens or ejaculatory ducts, history of spermatogenesis arrest, Sertoli cell syndrome, or post vasectomy.

Hypospermia indicates a decrease of semen volume to less than 2 mL per ejaculation.

Hyperspermia indicates an increase of sperm volume to more than 8 mL per ejaculation.

Oligozoospermia indicates a concentration of less than 20 million sperm/mL.

Asthenozoospermia indicates sperm motility of less than 50%.

Teratospermia indicates an increased number of abnormal sperm morphology at the head, neck, or tail level.

Evaluation of the female partner
Several congenital or acquired conditions affect female reproductive function. These conditions alter either the anatomy or the normal physiology of reproduction and may impair the transport of the gametes or embryo(s) and/or interfere with implantation and embryo/fetal development.

A complete evaluation of the female reproductive tract must include cervical, uterine, endometrial, tubal, peritoneal, and ovarian factors.

MENSTRUAL CHART

Cervical factors

The uterine cervix plays a crucial role in the transport and capacitation of the sperm after intercourse. The cervical factor accounts for 5-10% of infertility. Cervical mucus production, amount, and characteristics change according to the estrogen concentration during the late follicular phase.

At the beginning of the menstrual cycle, cervical mucus is scanty, viscous, and very cellular. The mucus forms a netlike structure that does not allow the passage of sperm. Mucus secretion increases during the mid follicular phase and reaches its maximum approximately 24-48 hours before ovulation.

The water and salt concentration increases, changing the physical characteristics of the mucus. It becomes thin, watery, alkaline, acellular, and elastic (spinnbarkheit) because of the increased concentration of sodium chloride, despite a fernlike pattern when the mucus is allowed to dry on a cover slide under the microscope

At this point, the mucus organizes itself, forming multiple microchannels so the spermatozoa can travel through. During this journey, the spermatozoa simultaneously undergo activation and capacitation. In addition, the mucus acts as a filter for abnormal spermatozoa and cellular debris present in the semen.

Cervical-factor infertility refers to abnormalities of the mucus-sperm interaction.

POST COITAL TEST

The Post Coital Test consists of evaluating the amount of spermatozoa and its motility within the cervical mucus during the preovulatory period. The couple is asked to have intercourse, without the use of lubricants, 8-12 hours before the test.

The mucus characteristics that determine a positive PCT test result are:

a volume of 0.3-1 mL,

spinnbarkheit greater than 10 cm,

a ferning pattern,

occasional cellularity,

a sperm count of 10-20 per high-power field.

Uterine factors

The uterus is the final destination for the embryo and the place where the fetus develops until delivery. Therefore, uterine factors may be associated with primary infertility or with pregnancy wastage and premature delivery. Uterine factors can be congenital or acquired. They may affect the endometrium or the myometrium and are responsible for 2-5% of infertility cases. Other problems affect the development and function of the endometrium.

Congenital defects: abnormalities of the the uterus can be responsible for implantation problems and first-trimester miscarriages.

Acquired defects

The endometrial lining constantly responds to the different hormonal secretions that occur during the menstrual cycle or to the exogenous administration of estrogen and progesterone.

Endometritis associated with a traumatic delivery, dilatation and curettage, intrauterine device, or any instrumentation (eg, myomectomy, hysteroscopy) of the endometrial cavity may create intrauterine adhesions or synechiae (ie, Asherman syndrome), with partial or total obliteration of the endometrial cavity.

Luteal Phase Defeciency

Intrauterine and submucous fibroids cause distortion of the cavity; compromise the blood supply; and are responsible for a lack of embryo implantation.

Diagnosis

Some defects can be detected during the pelvic examination. These include absence of the vagina and uterus, vaginal septum, and the presence of fibroids. Detection of most defects requires ancillary studies such as HSG, pelvic ultrasound, hysterosonogram, and MRI. Operative procedures, such as laparoscopy and hysteroscopy, are often necessary for confirmation of the final diagnosis.

Hysterosalpingogram (HSG)

The HSG is the most frequently used diagnostic tool to evaluate the endometrial cavity. A well-executed procedure, performed under fluoroscopy, provides accurate information about the endocervical canal; diameter and configuration of the internal os; endometrial cavity; uterotubal junction ; diameter and position of the fallopian tubes; status of the fimbriae; and spill into the endometrial cavity. Furthermore, the HSG provides indirect evidence of pelvic adhesions and uterine, ovarian, or adnexal masses.

Ultrasound

Pelvic ultrasound is an important tool in the evaluation and monitoring of infertile patients, especially during ovulation induction.It allows a precise evaluation of the position of the uterus within the pelvis and providing information about its size and irregularities. Pelvic ultrasound images also help in the early detection of uterine fibroids and endometrial polyps and help demonstrate the presence of ovarian cysts, adnexal masses, and endometriomas. Ultrasound helps in the diagnosis of anovulation, polycystic ovaries, and persistent corpus luteum cysts.

As a diagnostic tool, the use of MRI has increased in recent years, although it should be limited to those patients in whom a definitive diagnosis cannot be ascertained based on conventional HSG, ultrasound, and hysteroscopy findings.

Hysteroscopy

Hysteroscopy is a method of direct visualization of the endometrial cavity. The instrument used has evolved from the historical cystoscope and is based on the same principles . The operative hysteroscope allows both the diagnosis and treatment of endometrial pathology.

Tubal factors

The fallopian tubes play an important role in reproduction. After ovulation, the fimbriae pick up the oocyte from the peritoneal fluid that has accumulated in the cul-de-sac. The epithelial cilia transport the oocyte up to the ampulla. The capacitated spermatozoa are transported from the endometrium through the cornual section and advanced through the fallopian tube down into the ampulla, where fertilization occurs. The embryo initiates its early cleaving stages and is propelled upward to arrive at the endometrial cavity at the blastocyst stage (i.e., 96-120 h after ovulation).

Abnormalities or damage to the fallopian tube interferes with fertility and is responsible for abnormal implantation (eg, ectopic pregnancy). Obstruction of the distal end of the fallopian tubes accounts for accumulation of the normally secreted tubal fluid, creating distention of the tube with subsequent damage of the epithelial cilia.

Other tubal factors associated with infertility are either congenital or acquired. Congenital absence of the fallopian tube(s) can be due to spontaneous torsion in utero followed by necrosis and reabsorption. Elective tubal ligation and salpingectomy are acquired causes.

The 2 most frequently used tests for diagnosis of tubal pathology are HSG and laparoscopy

Peritoneal factors

The uterus, ovaries, and fallopian tubes share the same space within the peritoneal cavity. The cul-de-sac is the reservoir for the peritoneal fluid that accumulates around the time of ovulation. The oocyte is released from the follicle and floats in the peritoneal fluid. The fimbriae of the fallopian tube pick up the oocyte within minutes after ovulation and transport it up to the ampullary portion, where fertilization occurs. This finely orchestrated mechanism is important for the normal reproductive process.

Anatomical defects and/or physiologic dysfunctions of the peritoneal cavity, including infection, adhesions, and adnexal masses, account for infertility. PID, peritoneal adhesions secondary to previous pelvic surgery, endometriosis, and ovarian cyst rupture all compromise the motility in the fallopian tubes or produce blockage of the fimbriae with development of hydrosalpinx. Large myomas, pelvic masses, or blockage of the cul-de-sac interferes with the accumulation of peritoneal fluid and interferes with the normal oocyte pickup mechanism. Periovarian adhesions that encapsulate the ovary interfere with the normal oocyte release at ovulation, becoming a mechanical factor for infertility.

Laparoscopy

Laparoscopy is indicated as the last test in the evaluation of infertility because of the risks, the need for anesthesia, and the operative cost. The only exception is when a known medical history directs attention to a pelvic factor as the cause of infertility. .

Ovarian factors

Oogenesis occurs in the ovary from the first trimester of embryonic life and is completed by 28-30 weeks of gestation. By then, approximately 7 million oocytes are present. Theie growth is arrested at the this stage .Subsequently, the number of oocytes decreases and at birth, the pool of oocytes is reduced to approximately 2 million. By menarche, approximately 500,000 oocytes are present. Those oocytes are used throughout the reproductive years until menopause.

The ovulatory process is initiated once the hypothalamus-pituitary-ovarian axis matures and FSH and LH, under the regulation of gonadotropin-releasing hormone (GnRH), acquire their normal secretory patterns. From the cohort of follicles available each month, only a single oocyte is selected, establishes dominance, and develops to the pre-ovulatory stage. During follicular development, the granulosa cells secrete increasing amounts of estradiol, which, initially, through down-regulation, decreases the secretion of FSH. However, later, through a positive feedback mechanism, oestrogen participates in the LH surge that triggers the ovulatory process, induces the resumption of meiosis by the oocyte, and stimulates the formation of the corpus luteum and subsequent progesterone secretion.

Ovulatory dysfunction is defined as an alteration in the frequency and duration of the menstrual cycle. A normal menstrual cycle lasts 25-35 days, with an average of 28 days. Failure to ovulate is the most common ovulatory problem. Absence of ovulation can be caused by primary amenorrhea or premature menopause, indicative of the depletion of oocytes or absence of the ovaries.

A determination of serum progesterone level below 2ng, an endometrial biopsy finding that shows a proliferative pattern, and pelvic ultrasound results that show absence of a follicle and/or a corpus luteum are better criteria for diagnosing lack of ovulation.

Treatment

A consultation with the infertile couple once the evaluation has been completed is imperative. A treatment plan is outlined according to the diagnosis, duration of infertility, and the woman's age. If pregnancy is not been established within a reasonable time, a different treatment plan is considered.

Male factors
Asthenospermia associated with varicocele is treated with varicocelectomy or with embolization of the spermatic veins. The initial result of the procedure is not detected before 3 months because spermatogenesis takes 72 days. If no improvement occurs (depending on the amount of functional sperm recovery after the sperm wash), the decision must be made to proceed with either intrauterine insemination IUI or IVF.

Oligospermia is the most frequent cause of male infertility. Its treatment depends on the etiologic factor, but, in many instances, the underlying cause remains unknown. Intracervical insemination ICI or IUI is the treatment of choice if more than 2 million sperm are recovered after the sperm wash.

Azoospermia treatment depends on the classification. If obstructive azoospermia and normal gonadotropin levels co-exists, sperm can be obtained through microsurgical epididymal sperm aspiration or testicular biopsy. Fertilization of the partners oocytes is performed using IVF/ICSI. In patients with non-obstructive azoospermia, retrograde ejaculation can be the etiologic factor. The treatment consists of recovering sperm from a urine sample collected immediately after ejaculation. Patients with azoospermia that is not amenable to IVF/ICSI treatment benefit from artificial insemination (AI) with donor sperm.

Patients whose reproductive tract and FSH, LH, and testosterone levels are determined to be normal can be treated empirically with cycles of medication. Improvement in the sperm count is a good sign, and the treatment should be continued. Checking testosterone levels is advisable because an elevation above the reference range has a negative feedback effect on sperm production. Depending on the sperm count, the couple is advised to have intercourse near the time of ovulation or to proceed with IUI..

Female factors

Treatment of cervical factors
An abnormal PCT result attributable to chronic cervicitis may be treated with antibiotics. Treatment of reduced/absent secretion of cervical mucus due to destruction of the endocervical glands can be done by intrauterine insemination (IUI).

Treatment of uterine factors
The treatment of uterine malformations depends on the severity of the problem. Those who do have fertility problems are treated according to the following guidelines:

Uterine anomalies,synechiae or polyp, can be corrected through operative hysteroscopy under general anaesthesia.Uterine are corrected using operative hysteroscopy.

Cervical incompetence - Cerclage

Damage/absence of fallopian tubes - In vitro fertilization

Myoma treatment

In general, small and asymptomatic myomas do not require treatment, but the patient should be periodically monitored. The fibroids are treated if they are associated with marked blood loss during menstruation or if they are causes of infertility. Three modalities are used to treat myomas: medical treatment, surgical treatment, and embolization.

Medical treatment is a temporary treatment, ideally used for patients who are close to menopause and/or candidates with great risk during major surgery. Disadvantages of this treatment are symptoms of menopause, osteoporosis, and recurrence of the myomas after discontinuation of the treatment.

Surgical treatment of myomas is indicated in cases of excessive uterine bleeding, and when the myoma is implicated in inferility.

supply in case the implantation of the embryo occurs at the septum level.

Surgical intervention

In many instances, more than one hysteroscopy is required for total resection.

Endometrial polyps are removed through operative hysteroscopy associated with a dilatation and curettage, if necessary.

Treatment of endometrial factors

The treatment of LPD should be oriented to treat the underlying factor; therefore, having a precise diagnosis of the ovulatory dysfunction is crucial.

Document the response to treatment of LPD by repeating the endometrial biopsy during the first cycle of treatment. The patient should continue the progesterone treatment for 2 weeks and should not discontinue the progesterone unless a pregnancy test result is negative. If the patient conceives during the treatment, continue progesterone until the 10th week of pregnancy. By this time, the placenta takes over the endocrine control of the pregnancy. Of the patients in whom the LPD treatment is adequate, 70% conceive during the first 6 months of treatment. If pregnancy has not occurred during that interim, further fertility evaluation is required to exclude other associated factors that interfere with the success of the treatment. Remember that other lethal factors account for RPL (eg, chromosome abnormalities), and the patient will have another miscarriage regardless of a corrected LPD.

Treatment of tubal and peritoneal factors

Because of the intimate relationship between the fallopian tubes and the other pelvic organs and because, in the great majority of the cases, peritoneal pathology involves tubal pathology, the treatments of these factors are discussed together.

Tubal obstruction and lysis of adhesions can be corrected through laparotomy, operative laparoscopy, and, in special circumstances, through operative hysteroscopy and tubal cannulation.

Laparotomy is indicated in patients with severe pelvic adhesions that compromise the bowel, ovaries, and tubes, with obliteration of the cul-de-sac.

Operative hysteroscopy associated with tubal cannulation is helpful to treat cornual obstruction.

Treat fimbrial phimosis and periadnexal disease with laparoscopy .

Treatment of hydrosalpinx (distal tubal obstruction) with salpingostomy can be performed through microsurgery or operative laparoscopy. The success of the procedure is related to the diameter of the hydrosalpinx and to the damage to the cilial epithelium. If the cilial epithelium has been destroyed, the outcome of the procedure is poor, and it is better to perform a salpingectomy in preparation for future IVF.

Treatment of cornual obstruction (proximal) by tubocornual anastomosis can be done., however if severe the best results are achieved through IVF.

Treatment of endometriosis

Endometriosis treatment may be divided according to the severity of the disease and patient needs. Four alternatives are currently available to treat endometriosis: expectant therapy, surgical intervention, medical treatment, and combined therapy.

Expectant therapy

Based on a complete workup with diagnosis of very early stages of the disease (minimal) in patients without clinical symptoms, ie, an incidental finding. A second-look laparoscopy is required for follow-up observation within 6-18 months considering the unpredictability of the disease and its tendency to advance over time.

Surgical treatment

This is directed at destroying the disease using electrocoagulation, laser vaporization, or endocoagulation

Laparotomy is used for the treatment of severe disease or if a need for hysterectomy arises.

Medical treatment

Medical treatment is directed toward reducing estrogen production by the ovary. Depending on the therapeutic agent and the duration of treatment, endometriosis can be treated with hormonal manipulation.

Combined therapy

Medical and surgical treatments are usually combined for the treatment of severe endometriosis.Ovulation induction and IUI are used after completion of the treatment in hopes of expediting the establishment of a pregnancy before relapse of the disease

Treatment of ovarian factors

Ovulation induction is the treatment for infertile patients who still have oocytes within the ovaries but in whom a dysfunction of the hypothalamic-pituitary-ovarian axis exists.

Normal infertile couple
The prognosis for the NIC is poor and unpredictable. Only 5-7% of NICs eventually achieve a pregnancy within 5 years. If pregnancy does not occur during the first 4 IUI cycles, other alternatives include IVF or any of the associated ART procedures.

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