Welcome to chapter 2. The following chapter is called "Indications For IVF". The author is Dr Kamini A. Rao.

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1 Welcome to chapter 2. The following chapter is called "Indications For IVF". The author is Dr Kamini A. Rao.

2 The indications for an IVF treatment have increased since the birth of the first IVF baby. The past three decades have witnessed significant advances in the field of assisted human reproduction. Following the remarkable perseverance and triumph of Robert Edwards, Patrick Steptoe, and Jean Purdy, numerous scientists and physicians from all over the world have worked to develop more effective and safer procedures to treat infertile couples. Along with improvements in the areas of ovarian stimulation, embryo culture, and cryobiology, we have seen the introduction of assisted fertilization through intracytoplasmic sperm injection, the development of techniques to remove and perform genetic analysis on polar bodies or blastomeres, and the enhancement of methods for assessing the viability of the developing embryo. The ability to transfer embryos as well as the screening for chromosomal and single gene defects prior the transfer have reduced the risk of many inherited diseases. Immunoassay technology provides detailed insight into the cellular processes involved in gene expression. 2

3 Today, nearly all forms of infertility can be treated with the aid of one of the the various techniques of assisted reproduction. Techniques, which are now responsible for the birth of many children worldwide. At the beginning, the main indication for IVF was the treatment of tubal infertility caused by blocked or damaged fallopian tubes. However, the treatment options provided by IVF quickly led to an extension of indications far beyond the range of surgery of tubal infertility with patent but diseased tubes, or polycystic ovarian disease and other idiopathic conditions. According to Cochrane database 2005, Pandian et al., role of IVF in unexplained infertility remains unproven. Recently FAAST trial, 2007 (RCT of CC/IUI versus IVF) has shown higher pregnancy rates in early IVF group and time required for conception was less Following the introduction of ICSI in the early 1990s, the debate between assisted reproduction and surgery was long over. Today, ICSI represent approximately 40% of all indications for assisted reproductive technology (ART). 3

4 The attention given to the role of the male factor as a cause of infertility has increased, particularly since the techniques of assisted reproduction used by biologists and gynecologists are able to detect many more cases with abnormal semen quality. If the number of motile sperm is below 1-2 million after sperm preparation, IVF is normally indicated. Treatments for otherwise unexplained infertility generally include intrauterine insemination, in combination with ovarian stimulation, in efforts to increase gamete density and cycle fecundity. IVF, the alternative treatment for unexplained infertility, also obviously negates any unrecognized contributing cervical factor. 4

5 In the future, IVF will be increasingly applied for indications other than infertility. The growing applications for pre-implantation genetic diagnosis (PGD) are associated with a new range of indications for IVF. IVF becomes a tool to enable PGD and thus helps to prevent certain hereditary disorders. In young patients with cancer who are planned for chemotherapy or radiotherapy, gametes can be cryopreserved for future use. In a small number of patient requiring gestational surrogacy, IVF is also indicated. 5

6 Intracytoplasmic sperm injection (ICSI) is a component of in vitro fertilization (IVF). It has been a standard clinical technique for many years, and is no longer considered to be experimental. Several studies have demonstrated the efficacy and short-term safety of ICSI (Palermo et al, 1996). It is utilized for the treatment of infertility caused by a male factor or selected female factors. These factors include, (but are not limited to) morphologic anomalies of the oocyte, limited number of oocytes, and anomalies of the zona pellucida. In addition, ICSI may be indicated for IVF treatment if polyspermy or poor fertilization occurred in a prior cycle where insemination alone was used. Furthermore, it is indicated if preimplantation genetic diagnosis (PGD) is planned, especially for single gene defects. Although ICSI has enhanced the fertility prognosis for couples with severe male factor infertility, the appropriate indications for ICSI remain controversial. Absolute indications for ICSI include the use of microsurgical (epidydmal or testicular) aspirated spermatozoa in azoospermic patients. However data indicate that ICSI offers no advantage over IVF in terms of pregnancy rates in cases of non-male factor infertility. 6

7 Tubal disease has always been the main indication for IVF all times as it accounts for 25-35% of the cases of infertility and is associated with an increased risk of ectopic pregnancy. There are no randomized controlled trials comparing pregnancy rates following tubal surgery or IVF. Therefore, the decision to carry out IVF rather than tubal surgery is mainly subjective although it is based on clinical assessment of severity of tubal damage, age of the patient, and the availability of specialized surgical services and IVF. 7

8 Treatments of infertility caused by tubal damage include reconstructive surgery or in IVF. Over the last decade, success rates achieved with IVF have increased progressively while those for tubal surgery have remained relatively stable. The extent of tubal disease and pelvic pathology are important factors in determining the prognosis for success after surgical intervention. Pregnancy outcomes after reversal of tubal sterilization relate to the type of procedure performed, the site of anastomosis, and postoperative tubal length. Experienced surgeons have reported live birth rates as high as 57% and ectopic pregnancy rates between 5% and 12% following a segmental resection and anastomosis. Microsurgery may be a reasonable alternative to IVF when attempts at proximal tubal recanalization are unsuccessful in younger women, but the relatively low monthly fecundability (3% to 4%), costs, morbidity, and longer convalescence associated with laparotomy make IVF the preferred choice in older women. 8

9 The definite cause of infertility cannot be found in all couples with fertility problems. The relative benefit of IVF compared to expectant management or IUI remains uncertain in unexplained infertile couples. Conventional infertility management has been shown to be more cost-effective than IVF in the treatment of unexplained infertility (Quaas et al, 2008). The prognosis for a given couple for a spontaneous pregnancy should be weighted against pregnancy chances after more invasive treatment strategies like IUI or IVF. 9

10 The most expensive, but also most successful treatment in cases of unexplained infertility consists of the spectrum of assisted reproductive technology including IVF, with or without ICSI. Therefore, IVF is the treatment of choice for unexplained infertility when the less costly, but also less successful treatment modalities have failed. A randomized controlled trial of clomiphene citrate/iui versus IVF (Fast Track and Standard Treatment [FASTT] Trial) has recently been completed. In this trial, Reindollar and colleagues studied 503 couples assigned to conventional infertility treatment or an accelerated track to IVF. All couples had unexplained infertility and underwent infertility treatment for the first time. Patients were randomized to receive either a conventional treatment regimen of 3 cycles of clomiphene/iui, 3 cycles of FSH/IUI, and up to 6 cycles of IVF or to receive an accelerated treatment course of 3 cycles of clomiphene citrate/iui and then up to 6 cycles of IVF. In the conventional arm, 247 couples underwent 646 clomiphene citrate/iui, 439 FSH/IUI, and 261 IVF treatment cycles; in the accelerated arm, 256 couples received 642 clomiphene citrate and 357 IVF cycles. As of April 2007, 43/232 (18.5%) of the women in the conventional arm became clinically pregnant after clomiphene citrate/iui, 43/170 (25.3%) after FSH/IUI cycle, and 71/111 (64%) after IVF. In the accelerated arm, 50/242 (20.7%) became pregnant after clomiphene citrate/iui and 117/171 (68.4%) in an IVF cycle. The median time to pregnancy in the accelerated arm was shorter than the conventional arm. 10

11 Polycystic ovarian syndrome (PCOS) occurs in approximately 60-70% of women with anovulatory infertility. Cumulative singleton live birth rates of up to 71% within two years can be achieved in this group of patients with classical induction of ovulation, applying clomiphene citrate as first-line and exogenous gonadotropins as second-line treatment. Those women who may benefit from IVF as first-line therapy can be identified by older age, and longer duration of infertility. 11

12 In couples presenting with mild male infertility, IUI with washed & prepared sperms can be an effective treatment. IVF is normally indicated if fewer than 1-2 million sperms are present after sperm preparation. The results of IVF in male factor infertility are determined primarily by the age of women, degree of sperm motility, sperm morphology and sperm concentration. Infertility due to obstructive azoospermia may be treated effectively by surgical reconstruction or by retrieval of sperm from the epididymis or testis, followed by IVF/ICSI. 12

13 Vasectomy is an elective surgical sterilization procedure for men that is intended to obstruct or remove a portion of both vasa deferentia, thereby preventing sperm from moving from the testes to the ejaculatory ducts. Although intended for permanent sterilization, vasectomy can be reversed in most men seeking to restore their fertility due to a change in marital status or reproductive goals. The highest technical success rates are achieved by experienced surgeons using microsurgical techniques (Meng et al., 2005). Among the 222 repeat vasectomy reversal procedures reported by the Vasovasostomy Study Group, sperm returned to the semen after surgery in 75% of men, and 43% of their partners subsequently conceived. 13

14 Severe endometriosis is associated with pelvic adhesions and a distortion of pelvic anatomy leading to a possible mechanic or anatomic disturbance of fertility. However, it is probable that endometriosis, even in a mild stage, may have a direct negative effect on oocyte development, embryogenesis, or implantation. 14

15 Patients with low grade endometriosis may be considered as having either tubal or idiopathic infertility. According to a meta-analysis (Barnhart et al. 2002) significantly lower fertilization, implantation and pregnancy rates were observed in endometriosis compared to tubal factor controls. 15

16 Since the advent of IVF for tubal pathologies, the various indications for IVF have expanded. IVF has become first line in treatment of severe male factor infertility. Newer indications such as surrogacy and PGD have been introduced. 16

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