Traditional management of infertility in the era of in vitro fertilization

The main character in the 19 th century Leo Tolstoy's “Family Happiness” comments “children perhaps - what can more the heart of man desire?” This sentiment seems to apply to both kinds of gender. A human reproduction is inefficient, with average cycle fecundity around 20%.[] Due to lifestyle changes and different sociological factors, couples in modern societies are increasingly delaying childbearing with an overall reduction in fertility rates.[] Although in some developed countries concern regarding the declining fertility rates has been raised, forecasting agencies like U.N. and Eurostat predict that the total fertility rate in most countries will rise in the decades ahead.[] Advances in artificial reproductive technology cannot compensate for the age-related decline in infertility.[] In vitro fertilization is the most successful treatment of both male and female infertility. First IVF child Louise Brown was born in 1978.[] More than 4 million children have been born since then. In some countries 1-4% of all children born annually are born as a result of IVF. Pregnancy rates of 35-40% have been achieved as newer techniques are constantly being introduced.[] Definition Infertility is defined as inability to conceive within a year of unprotected intercourse.[] Causes of Infertility Essential Work-up for Infertile Couple Male factor - 35%[] Tubal and pelvic pathology - 35% Ovulatory dysfunction - 15% Unexplained infertility - 10% Unusual problems - 5%. Assessment of Male Factor for Infertility Semen analysis[] Assessment of ovulation Tubal patency tests. Semen analysis remains the main diagnostic test. It is carried out according to the methods suggested by WHO - 2010.[] Although many newer tests are available for sperm function, they are not yet established due to the lack of randomized controlled trials. Treatment of Male Factor Infertility Smoking cessation and antioxidant supplementation can be proposed.[] In cases of moderate to mild male-factor subfertility intrauterine insemination should precede IVF.[] Fine-needle aspiration of the motile spermatozoa can be done from testis or epididymis for intracytoplasmic sperm injection (ICSI) in cases of nonobstructive or obstructive azoospermia.[] Management of Ovulatory Infertility Optimization of body weight is the first line of treatment in underweight and in obese patients.[] WHO Classification of Ovarian Disorders If the cause of hypogonadotrophic hypgonadism can be found it should be treated - for example, surgery for intracranial tumors, otherwise women with hypogonadotrophic anovulation can be treated with pulsatile GnRH therapy. Gonadotrophin preparations containing both FSH and LH can also be used. WHO group 1 - hypogonadotrophic hypogonadism WHO group 2 - normogonadotrophic normogonadic ovarian dysfunction WHO group 3 - hypogonadotrophic hypogonadism Clomiphene citrate should be the first choice of treatment for normogonadotrophic anovulation. Dosage can be gradually increased monthly from 50 mg/day to 150 mg/day for 5 days. Treatment is generally for 6 months but can be extended to 12 months on individual basis until pregnancy occurs. Tamoxifen or letrazole can also be used as alternatives. In women with polycystic ovary syndrome who are resistant to clomiphene, cotreatment with metformin can be an alternative option. But routine use of metformin is of limited efficacy. A chronic low-dose step-up approach with gonadotropins is recommended for women with PCO who fail to conceive with the above treatment. Laparoscopic ovarian drilling can be an alternate to gonadotrophins.[] Treatment with donor oocyte is the only option for women with ovarian failure-hyper gonadotrophic hypogonadism For WHO - group 3, dopamine agonist is the treatment of choice for anovulation due to hyperprolactinemia. It can be combined with antiestrogens or gonadotropins in women who still fail to ovulate. Surgery in the Era of IVF Reproductive surgery can be Surgery as a Primary Treatment of Infertility Surgery as a primary treatment of infertility Surgery to enhance IVF. Laparotomy has been replaced by laparoscopy and hysterectomy. Peritoneal and tubal factors can be investigated by transvaginal ultrasound. Suspected endometriomas can be diagnosed by MRI although it is not cost-effective. Diagnostic laparoscopy is not useful as a routine procedure for infertility work-up. But on the other hand, laparoscopy for the surgical procedure for treatment of infertility is quite useful.[] A normal uterine cavity is a prerequisite for implantation. Hysterosalpingography and hysterosonography are useful to evaluate the uterine cavity besides giving information regarding the tubal patency. There is no place for routine hysteroscopy in the investigation of infertility except when intrauterine lesion is suspected. Common Laparoscopic Surgeries for Infertility Hysteroscopic surgeries for infertility could be hysteroscopy - polypectomy, myomectomy, metroplasty, and hysteroscopiclysis of intrauterine adhesions.[] Laparoscopic tubal surgeries like salpingostomy, fimbrioplasty, and end-to-end anastomosis of the fallopian tube Laparoscopic treatment of ovarian endometriomas Role of laparoscopic ablation of stage 1 and 2 endometriosis is limited as it does not contribute in increasing the pregnancy rate significantly. Treatment of Ovarian Endometriomas Endometriomas cause damage to ovarian reserve and function. Endometriomas less than 4 cm need no surgery. The stripping technique through laparoscopy is the common surgical procedure. Fenestration and ablation are the other techniques used. But excision of the endometrioticcyst >4 cm gives a higher pregnancy rate and lower recurrence rate. Irrespective of the type of procedure used there appears to be consequences on the ovarian reserve and menstrual function.[] Sparing the surgical procedure and going directly to IVF reduce the time to achieve pregnancy. The surgical procedure should be reserved for patients with pelvic pain and when it is difficult to access follicles for IVF.[] Unexplained Infertility Unexplained infertility is an inability on part of clinicians to identify a definite barrier to conception. The incidence of unexplained infertility is about 22-28%. Expected management has an important role to play in couples with unexplained infertility of short duration. Recent trials have questioned the effectiveness of empirical treatment with clomiphene citrate and IUI in the treatment of unexplained infertility.[] Superovulation plus IUI is a more effective treatment but is associated with higher rates of multiple pregnancy.[] For long-standing unexplained infertility, IVF is a better option.[]

Lifestyle changes and different sociological factors like delay in childbearing seem to contribute to the rate of declining fertility especially in developed countries. Hence there is an increasing demand for assisted reproductive technology. Due to newer more effective technologies, pregnancy rates of 35-40% have been achieved by IVF. Expectant management and ovulation induction with clomiphene citrate should be the first line of treatment in couples with infertility. Superovulation with IUI is a better option than IUI alone. Women with polycystic ovaries can be treated with clomiphene citrate initially. Gonadotrophins or laparoscopic ovarian drilling, if clomiphene citrate fails. Routine use of metformin treatment has limited place, but it can be used as a cotreatment with clomiphene citrate as a second option. The role of hysteroscopy and laparoscopy has a limited place in diagnostic procedures in infertility. They are useful in fertility enhancing surgical procedures like hysteroscopicpolypectomy, myomectomy, metroplasty, intrauterine adhesiolysis, and laparoscopy can be used for tubal anastomosis, salpingectomy, and fimbrioplasty. Ovarian endometriomas >4 cm should be operated. Laparoscopic surgical excision of endometriomas has a pregnancy rate of 50-66.7%. Laparoscopic surgery for endometriosis is mainly limited to the treatment of pelvic pain. For 22-28% of patients with unexplained infertility, if IUI with superovulation fails, IVF is the treatment of choice. Source of Support: Nil Conflict of Interest: No conflict of interest.

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