What do we mean by infertility?

Infertility is defined as inability to conceive even after unprotected and timely, time intercourse over a sustained period of time. So, it is an inability of a couple to conceive of pregnancy even after a certain period of timely and unprotected sexual intercourse. What the specified time interval define? If a women is of 35 years of age and less than that, then it is 12 months and if the women age is more than 35, it is 6 months.

What are the types of infertility?

It can be primary infertility, secondary infertility and unexplained. What do we mean by primary infertility? Here, the couple has never conceived and they are not conceiving it.

What is about secondary infertility?

Prior pregnancy is there, but this time the couple is not able to conceive. And unexplained where is, where the parents, where the couple is not able to conceive even any cause is not being identified. So, it is an unexplained infertility.

How common is infertility?

Well, infertility affects, can affect male as well as female. So, there are certain male factors for infertility, there are certain female factors for infertility or both factors can be shared, can be there in the same couple. Infertility is very common, around 48 billion couples live with infertility around the world.

So, coming to the male infertility, what are the causes of infertility in men?

Number 1, poor quality semen. The sperm count can be low or there have been no, there may be no sperm count or oligos, oligospermia where there is low sperm count in the semen or azoospermia where there is no sperm count. Sperm cannot, may not move properly, so there is motility problem in the sperm.

There can be abnormal sperm, the shape of the sperm can be abnormal. Testicular cause may be there like an infection in the testicle, testicular cancer, there is an injury or any surgery on the testicles. There can be congenital disorders and undescended testes.

Sterilisation procedure has been carried out, carried out in the male prior, that is vasectomy has been done that may cause male infertility. Ejaculation disorders can be there. Hypogonadism due to low testosterone level like in case of tumour, illegal drug use and clean filter syndrome.

Certain drugs can cause male infertility that includes sulfasalazine, anabolic steroids, chemotherapy and herbal medicines. Now, how to go about in case of male infertility? The investigation of choice is semen analysis to look for the quantity of semen, sperm count, sperm motility and sperm morphology. Certain criteria has been laid down by WHO to indicate the abnormality in semen.

Endocrine evaluation may be done which include follicle stimulating hormone, luteinizing hormone and testosterone, oestrogen, prolactin and thyroid stimulating hormone. Genetic testing can be done to look for the congenital cause like karyotyping, Y micro deletions and CFTR mutation gene. Imaging study like sproutal ultrasound, transabdominal ultrasound and transrectal ultrasound can be done to look for the anatomical cause and testicular biopsy particularly in testicular atrophy when the sperm has to be retrieved from the testicle.

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Now, what are the treatment?

Treatment depend on the aetiology and particularly in 40 to 50 percent of the men with infertility the cause is unidentified. Like if a patient is suffering from varicocele. Varicocele is the most common cause of male infertility. So, if a patient is suffering from varicocine, corrective surgery can be done.

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When the semen analysis is abnormal, the person should be referred to a male infertility specialist. When anatomical variance or abstraction is suspected, surgical counselling, surgical referral should be done. If an endocrinopathy such as hyper prolactinemia is seen, it should be corrected.

In patient with varicocine, well corrective surgery can be done, but it does not improve the pregnancy outcome despite improvement in the semen analysis result. Other treatment that include, they include basically chlormyphine citrate that is anti-oestrogen and gonadotrophin therapy. Use of antioxidants is there for improving male infertility like zinc, coenzyme Q, lycopene, L-carnitine and others.

Although intrauterine insemination, what do we mean by intrauterine insemination, is basically inoculation of sperm within the uterus. So, although intrauterine insemination has been shown to be equally effective as timely intercourse in unstimulated cycles, there is modest increase in live birth rate when combined with ovarian stimulation. By ovarian stimulation, we mean, we basically mean therapy to induce ovulation in the ovary.

In vitro fertilisation with or without intracytoplasmic sperm injection is the main stage of assisted reproductive technology for male factor infertility. Now, what are the medical treatments available? So, in case of male infertility, number one antibiotics particularly in case of vestibular infection, number two gonadotrophin therapy can be used, androgen therapy like testosterone, chlormethine citrate and lastly antioxidant. Coming to the gonadotrophins, we know anterior pituitary, they secrete two types of hormones, FHS and LH.

FHS basically, they cause, they support spermatogenesis and they have got trophic influence on the seminiferous tubules and absence of FHS that lead to testicular atrophy. What is the role of luteinizing hormone? Luteinizing hormone basically, they stimulate secretion of testosterone from the interstitial cells of lady and hence they are also called interstitial cell stimulating hormone. Now, in presence of hypogonadotropic, hypogonadism that means the deficient secretion of gonadotrophin in the body, in male they manifest as delayed puberty, number one, number two defective spermatogenesis leading to oligospermia, azoospermia and finally male sterility.

Now, in those cases, generally sexual maturation induced by androgen therapy and when the fertility is desired, in when the fertility is desired, human chorionic gonadotrophin is injected at a dose of 1000 to 4000 international unit 2 to 3 times a day and after 3 to 4 months of therapy, the dose is reduced and FHS 75 international unit with LH 75 international unit called menotropins is given. The treatment is continued for a total of 6 to 12 month duration and the response is satisfactory. Allergic reactions may be seen, skin pressure advised, hormonal malignancies should be ruled out before the therapy, other side effects are edoema, headache and mood changes.

Coming to testosterone therapy, we all know testosterone, they are secreted by interstitial cells under the pulsatile release of the gonadotrophins LH from the pituitary. Now, testicular failure may be primary, may be secondary, primary means from birth, so in children resulting in the delayed puberty. Now, in those cases, testosterone therapy can be given parentally or via transdermal group for a duration of 4 to 6 months.

Secondary testicular failure occurring later in life generally manifest as basically loss of libido, muscle mass, energy, anaemia and impotence. These are corrected gradually over a month with testosterone therapy. Now, coming to chlormyphine citrate, we all know it is an anti-oestrogen, they are oestrogen receptor antagonists.

Now, chlormethine increases gonadotrophin secretion and thus they are promoting spermatogenesis and testosterone secretion. For male infertility due to oligospermia, chlormethine citrate can be given in a dose of 20 mg daily for a duration of 24 days in a month with a rest of 6 days and it can be given for up to 6 months. However, the success rate is low.

Coming to the antioxidants, basically these drugs are decreasing the oxidative stress in the semen and thus are responsible for better sperm quality. Now, the most commonly used antioxidants are coenzyme butane, folic acid, L-carnitine, lycopene, N-acetyl cysteine, vitamin C, vitamin E, selenium and zinc. Coenzyme butane basically they reduce organic peroxide in the sperm or in the semen and thus they are improving the sperm quality.

The usual recommended dose is 300 mg daily. L-carnitine basically they increase the fatty acid transport into the sperm and thus they are increasing availability of epidermal sperm energy. Now, they increase sperm motility, morphology, maturation.

Coming to lycopene, it is a carotenoid basically antioxidant giving colours to the vegetables and fruit, pink, yellow, orange or red. It is a powerful antioxidant shown to improve the male fertility and significantly improve the semen parameters. Selenium basically when combined particularly with N-acetyl cysteine, they are responsible for improving sperm quality.

They are critical for biosynthesis of testosterone and sperm production. In a dose of 200 mg daily, it can be combined with vitamin E even 400 internationally. Coming to the female infertility, what are the causes? Number one very important cause is ovulation disorders that include polycystic ovary syndrome where there are multiple cysts in the ovary.

It can be due to thyroid disorders or ovarian failure. Now, secondly, scarring from surgery which result from pelvic or cervical injury surgery. Cervical mucus problems can be there because during the time of conception basically the sperm should penetrate the cervical mucus.

Uterine factors like fibroids, some congenital abnormalities can be the cause. There can be tubal factors like tubal block, endometriosis, pelvic inflammatory disease, sterilisation procedures already have been carried out. Drugs like NSAID, chemotherapy, neuroleptic medicines, spironolactone, illegal drug use.

Now, ovulation disorders have been categorised by World Health Organisation in the three groups. WHO group 1 is basically caused by hypothalamic pituitary failure. It is seen in 10 percent of the cases where the gonadotropin level in the body is low.

So, they present with amenorrhoea and low gonadotropin levels. They are most commonly seen in patients with low body weight and doing excessive exercise. Group 2 ovulation disorder the result from the dysfunction in the hypothalamic pituitary ovarian axis.

It is the most important cause seen in 85 percent of the cases. They are seen in patients with polycystic ovary syndrome and hyperprolactinemia. It is this group where ovulation induction with clomiphene citrate and basically gonadotrophins show a better prospect.

Group 3 is caused by ovarian failure in 5 percent of the cases. They can conceive only with oocyte donation and in vitro fertilisation.

What are the investigations?

To assess the ovulation, we do progesterone. So, ultrasound failures on the day 12 of cycle. Fever factors can be seen with uterosalpingography, laparotomy with dihydrotubation. Uterine factors can be seen by hysteroscopy, FSS, LS, testosterone, prolactin, PSS, DHEA, DHES and progesterone.

Progesterone basically is seen to look for the ovulation is occurring or not. Now, treatment of anovulatory disorders. Women with WHO group 1 ovulatory disorders they benefit from weight loss.

So, the patient is to have a normal body weight. Patient may be referred to a specialist for pulsatile administration of GNRH or the combination therapy with gonadotropin with LH. Women with group 2 basically they also benefit from weight loss, exercise and lifestyle modifications.

Chlamyphene citrate can be given to this group of ovulation disorders to improve the ovulation. Metformin can be added because that increase ovulation and pregnancy rate. Now, treatment for unexplained infertility.

In them the couples first should be advised to have a timely intercourse and that can be improved by use of urinary LH kit. What does it show? It shows the LH surge that precede the that precede 1 or 2 days before ovulation. Now, it can be done in a midday or evening urine specimen that improve the efficacy.

Other low-cost methods are basal body temperature measurement because it is seen during ovulation that rises and cervical mucus change. However, any of these procedure or any of these techniques does not increase the pregnancy rate and a simple recommendation to have a vaginal intercourse every 2 to 3 days to optimise the chance of pregnancy is there. Now, patients should be counselled that 50 percent of the couples who have not conceived in the first year have a chance to conceive in the second year.

Couples with unexpected infertility may want to consider another year of intercourse before moving to the more costly and invasive therapy that is assisted reproductive technology. Intrauterine insemination ovulation induction do not result in increased pregnancy rate in women with unexplained fertility and definitely in vitro fertilisation is used. Induction of ovulation how it is done? Ovulation induction can be performed using anti-oestrogen medication that include clomiphene citrate tamoxifen and use of exogenous gonadotropin.

What does it cause?

They cause stimulation of one or more ovarian follicles at a time. Now, coming to clomiphene citrate we all know they are oestrogen receptor antagonist they act on oestrogen receptor alpha and beta. Now, the chief use of clomiphene is for infertility due to failure of ovulation where it is used in a dose of 50 milligramme daily starting from the fifth day of cycle and is used for a period of five days.

Conception occurs in many women who previously were amenorrheic or had an ovular cycle. If there is failure of conception in one or two months of therapy the dose can be doubled and no more than six cycle treatment should be used. Addition of minotropins or human chorionic gonadotropins at the last two days of the course improve the success rate.

Coming to the gonadotropins, gonadotropins should be used in patients who have low gonadotropin level and in whom clomiphene citrate has not resulted in the improved ovulation. So, you know ovulation with clomiphene citrate have failed. The what the procedure we basically inject minotropins IM daily for 10 days followed by the next day either human chorionic gonadotropin 10,000 international unit.

Ovulation occurs in the next 24 to 48 hours in up to 75 percent of the cases and the women may conceive. However, rate of abortion and multiple pregnancies are high with ovulation induction to improve predictability of the time of ovulation and to for controlled ovarian hyperstimulation basically some experts they suppress the endogenous FSS LS secretion from the anterior pituitary by the use of continuous GNRS agonist or by the use of GNRS antagonist. Minotropins is also used in in vitro fertilisation to induce ovulation.

They have been used to induce simultaneous maturation of several ova and to precisely time ovulation in in vitro fertilisation so that several ova can be retrieved from the follicles. Ovarian hyperstimulation syndrome is a dangerous complication of ovarian induction is a potentially serious side effect that result in large ovarian cyst. There is increased capillary permeability leading to ascites, neural effusion, intravascular hypovolemia from which it may occur.

The condition is particularly found in polycystic ovarian disease patients and in elderly subjects. Mild cases respond to conservative treatment and no further ovarian stimulation. It is a couple with 12 month of infertility.

What we do?

We simultaneously evaluate male and female. Male evaluation is done by semen analysis. If it is normal we look for the other causes.

If it is abnormal we refer to the male fertility specialist. For the female evaluation what we do? We we see the ovulation is occurring or not first. So, we measure at 21 at day 21 posited on level.

If it is less than 5 that means ovulation is not occurring. So, we look for TSS, cold actin, FSS and estradiol level. If we get a cause we treat it consider ah we consider ovulation induction in WHO group 2 ovulatory disorder patient with clomiphene citrate or gonadotrophin and we assess the need for assisted reproductive techniques.

If the progesterone level is more than 5 that means ovulation is occurring we look for tubal cause and uterine cause. Surgical correction of tubal obstruction and uterine and we assess the need of ART that is all. And lifestyle factors all couples should be counselled to abstain from tobacco, limit the alcohol consumption and definitely maintain the body mass index at less than equal to 30 kg per metre square to improve their chances of natural conception number 1 and number 2 to improve the success rate of ah assisted reproductive techniques.

Obesity impairs fertility rate and the response to the fertility treatment including in vitro fertilisation. Therefore, it is advisable to counsel patients who are obese to lose weight before conception or in fertility treatment.