Committee opinion: role of tubal surgery in the era of assisted reproductive technology

There is a need to determine the optimal treatment methods for patients with tubal factor infertility. This document reviews the available treatments and discusses factors that must be considered when deciding between surgical repair versus in vitro fertilization. This document replaces the 2008 document of the same name.     

Role of varicocele repair for male infertility in the era of assisted reproductive technologies

Varicocele is an abnormal condition characterized by dilatation of the pampiniform plexus veins draining the testis and is present in 15 % of men. Varicoceles have an adverse effect on spermatogenesis and are the most common cause of male infertility. Approximately 35 % of infertile men and more than 70 % of men with secondary infertility were reported to have varicoceles. Although data on methods of varicocele repair are accumulating, there remains controversy regarding the indications and techniques for varicocele repair. In addition, the role of varicocele repair in this era of assisted reproductive technologies continues to be debated. In this study, we performed a comprehensive PubMed search in order to review the current status of varicocele repair for male infertility. We reviewed English‐language studies published from 1992 through 2013. After reviewing the articles, we identified a recent meta‐analysis of four randomized controlled trials, which found that varicocele repair for oligozoospermic men was associated with better pregnancy rates as compared with observation. Our review of prospective studies showed that all semen parameters, including sperm concentration, motility, and progressive motility, were significantly improved after varicocele repair. We also summarize the findings of recent studies reporting beneficial effects of varicocele repair, i.e., decreased oxidative stress and sperm DNA fragmentation after varicocele repair and superior cost effectiveness versus in vitro fertilization/intracytoplasmic sperm injection alone, which may be important in the era of assisted reproductive technologies. Varicocele repair is a widespread, well‐established procedure that can improve semen parameters in men with infertility. The effect of such treatment on the pregnancy rate is unclear because evidence is limited due to difficulties in recruiting patients for studies. Among the repair techniques, microsurgical repair using a subinguinal approach is potentially the best practice, although this procedure requires training in microsurgery. All these topics require further research in studies with sufficient patient enrollment and follow‐up.     

Ultrasound in assisted reproductive technology

Transvaginal ultrasound-guided oocyte retrieval is the gold standard for in vitro fertilization (IVF) treatment. Despite its relative safety, oocyte retrieval is associated with risk to the adjacent pelvic organs, bleeding, and pelvic infection. The embryo transfer (ET) procedure is considered a crucial step in an IVF cycle. The success of the ET is dependent upon multiple factors including embryo quality, proper endometrial receptivity, and the technique by which the embryos are transferred. Optimizing the technique of ET would therefore provide the best chance for pregnancy. No standard evidence-based protocol exists, but ET with ultrasound guidance has been shown to significantly increase the chance of embryo implantation, an ongoing pregnancy, and a live birth and to improve the ease of transfer. Identifying appropriate ultrasound-guided simulation training techniques in ET would ensure adequate fellowship training without affecting the outcome of assisted reproductive technology cycles.     

Epigenetics in assisted reproductive technology

It has been reported that the rates of epigenetic disorders such as Angelman syndrome (AS) and Beckwith–Wiedemann syndrome (BWS) are high in offspring conceived by assisted reproductive technology (ART). Angelman Syndrome is characterized by intellectual disability and BWS is known as large offspring syndrome (LOS). Weight abnormalities have also been reported in cloned animals. Possible factors underlying these findings include inherent gamete characteristics, influence of in vitro culture and peculiarity of ART methods. It is important to conclusively determine whether such epigenetic abnormalities are present in children conceived by ART, so as to consider the health of next generations.     

Reversal of tubal sterilization versus IVF in the era of assisted reproductive technology: a clinical dilemma

Two treatment options are available to women who wish to become pregnant after having had tubal sterilization: microsurgical reversal or IVF. The first approach is designed to restore tubal function, whereas the second replaces it. The first, to be successful, requires the presence of sufficient tubal length and normal or treatable fertility parameters. Treatment should therefore be individualized, based upon the findings of the couple's investigation, their wishes and the costs involved. The age of the female is the most important factor that affects the outcome with both treatment options. The live birth rate per cycle with IVF is 28%, but only 65.8% are singletons; 31.0% are twins and 3.2% triplets or more. Microsurgical tubal anastomosis yields a birth rate that exceeds 55%, without increased risk of multiple pregnancy. It offers the couple multiple cycles in which to achieve conception naturally, and the opportunity to have more than one pregnancy from a single intervention. The real dilemma lies with the 'industrialization' of IVF, and its frequent use as primary treatment for infertility. The dilemma is heightened by the fact that reconstructive tubal microsurgery is being taught and practised less and less, thereby eliminating this credible surgical option in most centres.     

Progesterone use in assisted reproductive technology

Progesterone is the main hormone in the luteal phase. It plays a key role in preparing the uterus for a possible pregnancy, and in maintaining it after it has occurred. In assisted reproduction treatments, there is usually a luteal phase deficiency, so it is necessary to supplement this critical phase to obtain the best results, not only of implantation but also of ongoing pregnancy. Among all the available options, exogenously administered progestogens are the most used, as they have proven their efficacy and safety. This review will address the most relevant aspects of luteal phase support with progesterone in the different scenarios an embryo transfer can be performed, such as the stimulated cycle, the artificial cycle, or the natural cycle. Although there is no evidence of the perfect protocol for all patients, recent studies point to the need of individualizing luteal phase support according to the needs of each patient.     

Role of embryo quality in predicting early pregnancy loss following assisted reproductive technology

Early pregnancy loss (EPL) significantly reduces the initial success rate of assisted reproduction treatments and increases the psychological burden on the patient. The aim of the current study was to investigate the association between embryo quality and EPL in IVF. A retrospective study of 1471 women undergoing IVF between July 2000 and October 2004 was performed. Multivariate logistic regression models evaluated the effect on EPL of the woman's age, type and cause of infertility, endometrial thickness on the day of oocyte retrieval, performance of intracytoplasmic sperm injection, number of transferred embryos, embryo quality as assessed by the number of blastomeres in the leading transferred embryo at day 3, and the percentage of fragmentation. The 2902 oocyte retrieval-embryo transfer cycles resulted in 816 pregnancies (28.1%; 705 women) constituting the study cohort. Of these, 259 pregnancies (31.7%) ended in EPL and 557 (68.3%) in ongoing pregnancies. EPL risk was significantly associated with advanced (>35 years) maternal age (OR=1.53; 95% CI 1.12-2.09) and five or fewer blastomeres in the leading embryo transferred at day 3 (OR=1.82; 95% CI 1.16-2.85). In conclusion, the quality of transferred embryos, as assessed by the total number of blastomeres in the leading transferred embryo, and maternal age are predictors of EPL.     

Outcomes from assisted reproductive technology

The use of assisted reproductive technology (ART) for treating the infertile couple is increasing in the United States. The purpose of this paper is to review the short-term outcomes after ART. Pregnancy rates after ART have shown nearly continuous improvement in the years since its inception. A number of factors affect the pregnancy rate, with the most important being a woman's age. Certain clinical diagnoses are associated with a poorer outcome from ART, including the presence of hydrosalpinges, uterine leiomyomata that distort the endometrial cavity, and decreased ovarian reserve. Multiple gestations are the major complication after ART. New laboratory techniques, including extended embryo culture, may allow the transfer of fewer embryos to maintain pregnancy rates while reducing the risk of multiple gestations. Although much of the morbidity in children born after ART is the result of multiples, recent analysis suggests that even singletons are at higher risk for perinatal morbidity, including preterm delivery and small for gestational age infants. In vitro fertilization may be associated with a slight increased risk for birth defects. The major short-term complication of ART in women is the development of ovarian hyperstimulation syndrome. This syndrome is difficult to predict, but new treatments are being developed that may limit its frequency. Because of its high pregnancy rate, couples are moving to ART more quickly in the management of their infertility. All outcomes of ART, including pregnancy rates and adverse complications, need to be compared with standard non-ART therapy when deciding the appropriate course of treatment for a given couple.     

Transparency of results in assisted reproductive technology

Clear results in ART need to take into account the technical performances of the centre but also patients selection, cycles cancelling and embryo transfer policies. The risk of a partial transparency is an inappropriate selection of patients. From classical criterias like pregnancies per oocytes retrievals or embryo transfers we are heading towards more global indicators like live births of singletons by initiated cycles rate.     

Microsurgical varicocelectomy in the era of assisted reproductive technology: influence of initial semen quality on pregnancy rates

OBJECTIVE: To evaluate the natural history of infertile couples in whom the man underwent varicocelectomy. DESIGN: Retrospective study. SETTING: University infertility clinic. PATIENT(S): 159 infertile couples. INTERVENTION(S): Microsurgical varicocelectomy. MAIN OUTCOME MEASURE(S): Standard semen parameters and pregnancy rates (assisted and unassisted). RESULT(S): Postoperative sperm concentration and motility increased significantly compared to before the varicocelectomy (28.9 +/- 3.0 vs. 22.5 +/- 2.1 x 10(6)/mL and 33.9 +/- 1.9 vs. 22.1 +/- 1.3%, respectively). Overall, 48% (76/159) of the couples achieved a spontaneous pregnancy at the mean of 30 months' follow-up. An additional 10% (16/159) and 11% (18/159) of couples achieved a pregnancy following intrauterine insemination and in vitro fertilization/intracytoplasmic sperm injection, respectively. Significantly higher spontaneous pregnancy rates were observed in couples in whom the man's initial sperm concentration was greater than or equal to 5 million sperm per milliliter compared to those in whom the man's initial sperm concentration was less than 5 million sperm per milliliter (61% vs. 8%, respectively). CONCLUSION(S): Our data demonstrate that, in couples in whom the man undergoes varicocelectomy for treatment of varicocele, close to 70% achieve a pregnancy. The initial sperm concentration is predictive of unassisted pregnancy outcome in this population.