|Infertility is a disease, defined as the failure to achieve a successful
pregnancy after 12 months or more of regular unprotected intercourse
. It is estimated that infertility affects 13% to 15% of couples
worldwide . Moreover, 20% of couples consult their general
physician because of difficulty conceiving, and half of those couples
(10%) require specialist care. In many cases, infertility can be effectively
treated only by means of assisted reproductive techniques (ART), which
comprises all fertility treatments in which oocytes, sperm and embryos
are handled. Since the first successful application of in vitro fertilization
in 1978, ART has become widely spread all around the world, and
more than 3 million of in vitro conceived babies were born. While we
celebrate the significant advances made in the field of ART, intensive
search for innovative approaches aimed at increasing birth rates and at
reducing the occurrence of complications associated to ART, mainly
ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies
|Ovarian stimulation is a key component of ART and is directed
towards the ultimate goal of obtaining an adequate number of good
quality oocytes while preventing excessive ovarian response. Recent
years have witnessed a significant expansion of the pharmacological
armamentarium useful in ovarian stimulation protocols. Introduction
in clinical practice of recombinant gonadotropins (FHS, LH, and hCG)
and GnRH antagonists are among the most remarkable in this respect.
Corifollitropin alfa is a long acting FSH analogue, able to initiate
and sustain multiple follicular growth for seven days. As remarkable
advantage, corifollitropin alfa may allow the development of simplified
treatment regimens with the increase in injection-free interval .
GnRH antagonists are used to prevent premature LH surges in women
undergoing controlled ovarian hyperstimulation for ART programs.
GnRH antagonists have been shown, in comparison to GnRH agonists,
to reduce significantly the risk of OHSS . This iatrogenic and
potentially life threatening condition, resulting from excessive ovarian
stimulation, is estimated to affect 1%-10% of ART cycles. GnRH
antagonists also contribute to OHSS prevention by allowing to trigger
ovulation with a bolus of a GnRH agonist as an alternative to hCG .
|The selection of embryos with maximal developmental and
implantation potential has relayed on morphological parameters and
cleavage rate, as assessed by light microscopy. This methodology has
many recognized pitfalls and shortcomings, as underlined by the
failure of approximately 8 of 10 transferred embryos to implant. Novel
technologies for non-invasive assessment of embryo viability in assisted
reproduction are under evaluation. The so called omics, including
genomic, transcriptomic, proteomic and metabolomic analysis
strategies are among the more innovative and promising . A factor
possibly implicated in the relative low implantation rate is the elevated
frequency of embryonic numerical chromosomal abnormalities.
Preimplantation genetic screening (PGS) aims at identifying viable
euploid embryos potentially having higher chances of producing a
pregnancy. The main indications for PGS are advanced maternal age,
repeated implantation failure, repeated miscarriage, and eventually
severe male factor infertility. Unfortunately there is no evidence of a
beneficial effect of PGS as currently applied of a beneficial effect of PGS,
as currently applied, on ART outcome . PGS clinical efficiency might
benefit of emerging novel technologies, including single nucleotide
polymorphism (SNP) and comparative genomic hybridization (CGH)
allowing the simultaneous enumeration of all chromosomes .
|Improvements in the field of cryobiology, with particular reference
to the introduction of the vitrification technique, have made possible
to efficiently preserve oocytes. Survival rates and clinical outcomes
comparable to those obtained with fresh oocytes in ART programs
have been recently reported . Although oocyte cryopreservation is
still considered experimental by major regulatory bodies in Europe and
United States, the favorable perspectives offered by this technology in
term of fertility preservation for reasons related to age, has led to the
extension of clinical application of oocyte freezing also to non-medical
indications. A debate regarding the potential social implications of this
emerging indication was recently sparked .
|Concerns regarding the human risk from ART have risen with the
advent of intracytoplasmic sperm injection (ICSI). The invasiveness
of this technique allowing the injection of the spermatozoon into
the oocyte, and thus circumventing all the natural selective barriers,
prioritizes the need for careful risk estimation. Although further
monitoring is required to draw firm conclusions, recent outcome
studies are partially reassuring. Only a slight increase in fetal
chromosomal abnormalities and congenital malformations has been
associated to ICSI . It is important also to note that emerging data
support the concept that ICSI-conceived boys are not at increased risk
of altered reproductive health, as reflected by salivary testosterone
concentrations measured in teenagers .
- Practice Committee of the American Society for Reproductive Medicine (2008) Definitions of infertility and recurrent pregnancy loss. Fertil Steril 89: 1603.
- Boivin J, Bunting L, Collins JA, Nygren KG (2007) International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod 22: 1506-1512.
- Ledger WL, Fauser BC, Devroey P, Zandvliet AS, Mannaerts BM (2011) Corifollitropin alfa doses based on body weight: clinical overview of drug exposure and ovarian response. Reprod Biomed Online 23: 150-159.
- Gilliam ML (2011) Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Obstet Gynecol 118: 706-707.
- Humaidan P, Papanikolaou EG, Kyrou D, Alsbjerg B, Polyzos NP, et al. (2012) The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives. Reprod Biomed Online 24: 134-141.
- Seli E, Robert C, Sirard MA (2010) OMICS in assisted reproduction: possibilities and pitfalls. Mol Hum Reprod 16: 513-530.
- Mastenbroek S, Twisk M, van der Veen F, Repping S (2011) Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update 17: 454-466.
- Gutiérrez-Mateo C, Colls P, Sánchez-García J, Escudero T, Prates R, et al. (2011) Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril 95: 953-958.
- Cobo A, Diaz C (2011) Clinical application of oocyte vitrification: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril 96: 277-285.
- Shkedi-Rafid S, Hashiloni-Dolev Y (2011) Egg freezing for age-related fertility decline: preventive medicine or a further medicalization of reproduction? Analyzing the new Israeli policy. Fertil Steril 96: 291-294.
- Van Steirteghem A (2012) Celebrating ICSI's twentieth anniversary and the birth of more than 2.5 million children--the 'how, why, when and where'. Hum Reprod 27: 1-2.
- Belva F, Bonduelle M, Schiettecatte J, Tournaye H, Painter RC, et al. (2011) Salivary testosterone concentrations in pubertal ICSI boys compared with spontaneously conceived boys. Hum Reprod 26: 438-441.