辅助生殖技术前应重视男性不育患者的常规处理

辅助生殖技术(assisted reproductive technique,ART)给男性不育症的治疗和预后带来了巨大改变,但ART前期是否有必要对男性不育开展常规处理存在广泛争议.本文介绍了ART前对男性不育症患者进行常规处理的意义,包括对男性不育常规治疗研究的深化和有助于ART的顺利成功开展.系统介绍了ART前男性不育常规治疗技术,包括药物、手术和实验室技术;常规药物治疗的可能环节与目的,包括确保有足够的精子用于ART,改善ART治疗结局、困难病例及ART失败后的再努力以及对男性不育症中性功能障碍的处理.     

Surgical management of tubal disease and infertility

With advances in assisted reproductive technology (ART), the role of reproductive surgery as the primary treatment of infertility has been questioned. Tubo-peritoneal factor infertility is common, and accounts for 30–40% of female infertility. The pathology of tubal disease ranges from peritubal adhesions, proximal and/or distal tubal blockage, hydrosalpinx to previous sterilization. In tubo-peritoneal factor infertility, reproductive surgery remains an important option and is complementary to ART. It should be considered as the first-line treatment if a good result is expected, when the pathology is treatable or if left untreated would adversely affect the results of ART. The success of reproductive surgery depends on careful patient selection using proper investigative tools, performed in units with expertise following microsurgical principles.     

Observation of spermatozoa by a high-magnification microscope

Semen analyses are the primary tool for evaluating male infertility, as semen parameters are useful for predicting potential fertility. In the field of assisted reproductive technology (ART), the single best motile spermatozoon should be selected, especially when performing intracytoplasmic sperm injection (ICSI). In this context, the motile sperm organelle morphology examination (MSOME) was developed as a method of assessing the detailed morphology of motile spermatozoa in real time at a magnification of up to 6,300× on a video system. The use of ICSI with MSOME-selected sperm is called intracytoplasmic morphologically selected sperm injection (IMSI). IMSI improves the outcomes of ICSI. MSOME can be also applied to evaluate male infertility. Among MSOME parameters, the presence of sperm nuclear vacuoles is the most important finding. Large sperm nuclear vacuoles (LNV) are related not only to poor ART outcomes, but also to poor semen quality and sperm DNA damage, such as DNA fragmentation and chromatin condensation failure. It has been suggested that sperm head vacuoles are produced at earlier stages of sperm maturation. It is possible that the number of LNV can be decreased by surgical or medical treatment for male infertility. Therefore, the level of LNV has the potential to be used as an alternative parameter of semen quality and a new tool for evaluating the therapeutic effects of treatment in male patients with infertility.     

Surgical management of tubal disease and infertility

With the advances in assisted reproductive technology (ART), the role of reproductive surgery as the primary treatment of infertility has been questioned. Tubo-peritoneal factor infertility is common, and accounts for 30–40% of female infertility. The pathology of tubal disease ranges from peritubal adhesions, proximal and/or distal tubal blockage, hydrosalpinx to previous sterilisation. In tubo-peritoneal factor infertility, reproductive surgery remains an important option and is complementary to ART. It should be considered as the first-line treatment if a good result is expected, when the pathology is amendable or if left untreated will adversely affect the results of ART. The success of reproductive surgery depends on careful patient selection using proper investigative tools, performed in units with expertise following microsurgical principles.     

ART: iatrogenic multiple pregnancy?

Assisted reproductive technologies (ART) are now widely accepted as effective treatment for most causes of infertility. With improving success rates, attention has turned to the problem of multiple pregnancies, which are associated with a poor perinatal outcome, maternal complications and significant financial consequences. The challenge is to reduce multigestational pregnancies while maintaining good treatment outcomes. Methods to prevent multiple pregnancy include restrictive use of ART in couples with a good chance of spontaneous pregnancy, cautious use of gonadotrophins, and increased use of natural-cycle intra-uterine insemination and elective single embryo transfer in in-vitro fertilization and intracytoplasmic sperm injection. The aim of this article is to review the contribution of fertility treatment to multiple pregnancies and strategies for reducing multiples in ART.     

Assisted reproduction and risk of preterm birth in singletons by infertility diagnoses and treatment modalities: a population-based study

Purpose

The purpose of this study is to examine the spectrum of infertility diagnoses and assisted reproductive technology (ART) treatments in relation to risk of preterm birth (PTB) in singletons.

Methods

Population-based assisted reproductive technology surveillance data for 2000–2010 were linked with birth certificates from three states: Florida, Massachusetts, and Michigan, resulting in a sample of 4,370,361 non-ART and 28,430 ART-related singletons. Logistic regression models with robust variance estimators were used to compare PTB risk among singletons conceived with and without ART, the former grouped by parental infertility diagnoses and treatment modalities. Demographic and pregnancy factors were included in adjusted analyses.

Results

ART was associated with increased PTB risk across all infertility diagnosis groups and treatment types: for conventional ART, adjusted relative risks ranged from 1.4 (95% CI 1.0, 1.9) for male infertility to 2.4 (95% CI 1.8, 3.3) for tubal ligation. Adding intra-cytoplasmic sperm injection and/or assisted hatching to conventional ART treatment did not alter associated PTB risks. Singletons conceived by mothers without infertility diagnosis and with donor semen had an increased PTB risk relative to non-ART singletons.

Conclusions

PTB risk among ART singletons is increased within each treatment type and all underlying infertility diagnosis, including male infertility. Preterm birth in ART singletons may be attributed to parental infertility, ART treatments, or their combination.

     

Causes spermatiques et échecs de fécondance : quelles explorations autres que le spermogramme ?

Conventional in vitro fertilization (cIVF) is an assisted reproductive technologies (ART) procedure, which requires both a sufficient number of motile sperm to be inseminated around the oocyte but also an optimal fertilizing ability of the inseminated sperm. Thus, the frequency of the risk that this method leads to a failure of fertilization varies depending on the cIVF indication and is enhanced if no factor of infertility was found in the first-line examination, suggesting a "qualitative" incapacity of the sperm to fertilize. Thus, many secondary sperm tests have been studied to know whether they could predict such fertilization failure The aim of this review is then to analyze the literature interested on these secondary specialized explorations sperm and their ability to predict the fertilization rate following cIVF, especially when an idiopathic (normal conventional sperm examination, including normal pelvic laparoscopy) or a pseudo-idiopathic infertility (normal conventional sperm examination, but non-done pelvic laparoscopy) are suspected.     

Depression in Chinese men undergoing different assisted reproductive technique treatments: prevalence and risk factors

Purpose

To explore the prevalence and risk factors for depression in men undergoing different assisted reproductive technique (ART) treatments in Chinese population.

Method

This was a prospective study of 844 men undergoing ART treatments. All men were distributed to four groups, according to they received treatments. The treatments included IUI (intrauterine insemination), IVF(in vitro fertilization), ICSI(intra cytoplasmatic sperm injection) and TESA/PESA (percutaneous epididymal sperm aspiration/testicular sperm aspiration). Their symptoms of depression were measured with use of the Center for Epidemiologic Studies of Depression scale(CES-D). Data were collected about age, BMI, education, duration of marriage, duration of infertility, smoking, type of infertility, infertility causes, history of ejaculation failure, and financial burden of the treatment. We estimated the prevalence of depressive symptom in men undergoing different ART and used logistic regression models to identify risk factors for depression in different groups.

Results

The overall prevalence of depression was 13.3 % for men undergoing ART treatments: 14.5 % of IUI group, 12.4 % of IVF group, 19.2 % of ICSI group and 6.2 % of TESA/PESA group. Prevalence of depression among IUI group, IVF group and ICSI group were not significantly different. For IUI group, the factors were found to increase depression risk were treatment financial burden and duration of marriage, to decrease depression risk was age. For IVF group, the risk factors independently associated with depression were both male and female infertility, unexplained infertility, and history of ejaculation failure.

Conclusion

In a sample of Chinese men undergoing ART treatments, the prevalence of depression was higher than other country. The risk factors for depression varied in different ART treatments groups. when routine screening to identify the sub-group of vulnerable men which need counselling before ART treatments, we should also consider which pattern of ART treatments the man underwent.     

Infertilit?t des Mannes

The reasons for male infertility can be endocrine, testicular and/or exogenous in origin. In depth diagnostic techniques aim to detect treatable causes and should include a review of the medical history, clinical and sonographical examinations, endocrinological tests and ejaculate analyses. If no medical or surgical treatment is applicable, methods of assisted reproductive fertilisation may be advisable depending on the female reproductive functions. Semen analysis gives details on sperm count, motility and morphology as well as infections, immunological factors and problems of the seminal ducts. Approximately 12% of patients are azoospermic. This severe form of male infertility mostly results from genetic disorders, and the most common numerical chromosomal disorder is Klinefelter??s syndrome. In cases of non-obstructive azoospermia testicular sperm extraction offers the chance for intracytoplasmic sperm injection in 50% of patients. In cases of obstructive azoospermia microsurgical reconstruction procedures are preferable to testicular sperm extraction.     

A renaissance in reproductive endocrinology and infertility

Assisted reproductive technology (ART) is catalyzing a renaissance in reproductive endocrinology and infertility (REI), manifested by the rapid growth of new technologies, such as intracytoplasmic sperm injection, oocyte cryopreservation, preimplantation genetic manipulation of embryos, and embryonic stem cell biology. Because of advances in ART, REI will be a vibrant and growing discipline, both in academic and independent practice settings, for many decades.     

Successful pregnancy in a liver transplant recipient following controlled ovarian hyperstimulation and intracytoplasmic sperm injection

As the demand for assisted reproductive technologies (ART) increases, infertility treatments are increasingly being sought by patients with serious health problems that were once regarded as leading to infertility. Moreover, since pregnancy may worsen their underlying health conditions, these women have been advised to remain infertile. We describe here a liver transplant recipient who underwent ART for male factor infertility. Assisted fertilization was achieved using intracytoplasmic sperm injection, and she conceived after embryo transfer. Her pregnancy follow-up was unremarkable until she delivered a healthy boy pretermly at 31 and half weeks.     

Severe male infertility after failed ICSI treatment-a phenomenological study of men's experiences

Background  

Male-factor infertility underlies approximately 30% of infertility in couples seeking treatment; of which 10% is due to azoospermia. The development of assisted reproductive technology (ART), enabling the use of epididymal or testicular sperm for fertilization of the partner's oocytes, has made biological fatherhood possible for men with obstructive azoospermia. There is limited knowledge of men's experience of their own infertility. The aim of this study was to describe men's experiences of obstructive azoospermia infertility.     

Perinatal outcome among singleton infants conceived through assisted reproductive technology in the United States

OBJECTIVE: To examine perinatal outcome among singleton infants conceived with assisted reproductive technology (ART) in the United States. METHODS: Subjects were 62,551 infants born after ART treatments performed in 1996-2000. Secular trends in low birth weight (LBW), very low birth weight (VLBW), preterm delivery, preterm LBW, and term LBW were examined. Detailed analyses were performed for 6,377 infants conceived in 2000. Observed numbers were compared with expected using a reference population from the 2000 U.S. natality file. Adjusted risk ratios were calculated. RESULTS: The proportion of ART singletons born LBW, VLBW, and term LBW decreased from 1996 to 2000. The proportion delivered preterm and preterm LBW remained stable. After adjustment for maternal age, parity, and race/ethnicity, singleton infants born after ART in 2000 had elevated risks for all outcomes in comparison with the general population of U.S. singletons: LBW standardized risk ratio 1.62 (95% confidence interval 1.49, 1.75), VLBW 1.79 (1.45, 2.12), preterm delivery 1.41 (1.32, 1.51), preterm LBW 1.74 (1.57, 1.90), and term LBW 1.39 (1.19, 1.59). Risk ratios for each outcome remained elevated after restriction to pregnancies with only 1 fetal heart or any of 7 other categories: parental infertility diagnosis of male factor, infertility diagnosis of tubal factor, conception using in vitro fertilization without intracytoplasmic sperm injection or assisted hatching, conception with intracytoplasmic sperm injection, conception in a treatment with extra embryos available, embryo culture for 3 days, and embryo culture for 5 days. CONCLUSION: Singletons born after ART remain at increased risk for adverse perinatal outcomes; however, risk for term LBW declined from 1996 to 2000, whereas preterm LBW was stable. LEVEL OF EVIDENCE: III     

Thoughts on the popularity of ICSI

PurposeIntracytoplasmic sperm injection (ICSI) is the most widely utilized assisted reproductive technique (ART) worldwide. In this feature, we review the early assisted fertilization attempts that eventually led to the development of ICSI, and discuss its current utilization in cases of male and non-male factor infertility.MethodsWe researched the literature related to the development, indications, and current use of ICSI, such as sperm structural abnormalities, male genetic indications, surgically retrieved sperm, high sperm chromatin fragmentation, oocyte dysmorphism, and preimplantation genetic testing (PGT). We also describe the potential future applications of ICSI.ResultsThis review summarizes the early micromanipulation techniques that led to the inception of ICSI. We also explore its current indications, including non-male factor infertility, where its use is more controversial. Finally, we consider the benefits of future advancements in reproductive biology that may incorporate ICSI, such as in vitro spermatogenesis, neogametogenesis, and heritable genome editing.ConclusionThe versatility, consistency, and reliability of ICSI have made it the most prevalently utilized ART procedure worldwide.     

Practice of assisted reproduction in Korea

Conclusion The developments in ART have enabled a broader range of infertility disorders to be managed by ART and made possible a customized approach to infertility management based upon defining the major factors underlying infertility and providing the most relevant treatment procedure to produce reliably satisfactory pregnancy rates.The results are likely to improve further by reducing the chance of canceled controlled ovarian hyperstimulation cycles, for example, improved ovarian responsiveness with growth hormone, by increasing the fertilization rate in severe male-factor cases with sperm enhancers and micromanipulation and by developing coculture and embryo cryopreservation.     

Surgically acquired sperm use for assisted reproductive technology: trends and perinatal outcomes,USA, 2004–2015

Purpose

To compare national trends and perinatal outcomes following the use of ejaculated versus surgically acquired sperm among IVF cycles with male factor infertility.

Methods

This retrospective cohort includes US fertility clinics reporting to the National ART Surveillance System between 2004 and 2015. Fresh, non-donor IVF male factor cycles (n?=?369,426 cycles) were included. We report the following outcomes: (1) Trends in surgically acquired and ejaculated sperm. (2) Adjusted risk ratios comparing outcomes for intracytoplasmic sperm injection (ICSI) cycles using surgically acquired (epididymal or testicular) versus ejaculated sperm. (3) Outcomes per non-canceled cycle: biochemical pregnancy, intrauterine pregnancy, and live birth (≥?20 weeks). (4) Outcomes per pregnancy: miscarriage (<?20 weeks) and singleton pregnancy. (5) Outcomes per singleton pregnancy: normal birthweight (≥?2500 g) and full-term delivery (≥?37 weeks).

Results

Percentage of male factor infertility cycles that used surgically acquired sperm increased over the study period, 9.8 (2004) to 11.6% (2015), p?<?0.05. The proportion of cycles using testicular sperm increased significantly over the study period, 4.9 (2004) to 6.5% (2015), p?<?0.05. Among fresh, non-donor male factor ART cycles which used ICSI (n?=?347,078 cycles), cycle, pregnancy, and perinatal outcomes were statistically significant but clinically similar with confidence intervals approaching one between cycles involving epididymal versus ejaculated sperm and between testicular versus ejaculated sperm. Results were similar among cycles with a sole diagnosis of male factor (no female factors), and for the subset in which the female partner was <?35 years old.

Conclusion

Among couples undergoing ART for treatment of male factor infertility, pregnancy and perinatal outcomes were similar between cycles utilizing ejaculated sperm or surgically acquired testicular and epididymal sperm.

     

Access to infertility care and ART treatment in India: A clinician's perspective

Infertility is a worldwide problem that is increasing with time. The cause of infertility can be due to either male or female factors or both. The food, environmental, occupational and psychological factors do contribute to infertility. The infertility and the present scenario of assisted reproductive technology (ART) in India with regard to the clinics, clinicians and regulatory mechanisms in vogue are discussed. The potential of India as a reproductive tourist destination and surrogacy issues is included. The social, economic, and family problems arising as a consequence of infertility are discussed. The status of ART in India is getting improved and the gap between the West and India is expected to be minimized with the influence of regulatory mechanisms introduced through ART Act in India. The salient features that have a bearing on the infertility treatment outcomes, which are being neglected, or recent findings of research are included with special reference to possible future developments in the field of ART.     

Children born after assisted reproductive technology

Since the birth of Louise Brown in July 1978 and the birth of the first intracytoplasmic sperm injection (ICSI) child in January 1992 many couples with longstanding female-factor or male-factor infertility can be helped to overcome their infertility resulting in a delivery and birth of a child. The final and ultimate goal of all infertility treatments has been to give the large population of infertile couples a chance to fulfil their childwish and experience the happiness of having a healthy child. Major advances have been made in the different treatment protocols for infertility during the last 25 years. It is, however, surprising that only a limited number of studies have been carried out assessing the health of the children born after ART. In this review we shall comment on the limitations of follow-up studies on ART children and we shall review existing data on the outcome of in vitro fertilization (IVF) and ICSI pregnancies. The most important outcome data consist of information on minor and major congenital malformations obtained prenatally or after birth, as well as on the further development of the children.     

In vitro fertilization for cancer patients and survivors

OBJECTIVE: To determine in vitro fertilization (IVF) outcome in cancer patients. DESIGN: Retrospective record review. SETTING: Academic, hospital-based assisted reproductive technology (ART) program. PATIENT(S): Sixty-nine women undergoing 113 IVF/gamete intrafallopian transfer (GIFT) cycles after cancer treatment in one partner, and 13 women undergoing 13 IVF cycles for embryo cryopreservation before chemotherapy/radiation. INTERVENTION(S): IVF, intracytoplasmic sperm injection (ICSI), assisted hatching, and gamete intrafallopian transfer as indicated. MAIN OUTCOME MEASURE(S): Delivery rate, spontaneous abortion rate, number of embryos cryopreserved, cancer diagnosis, systemic or local cancer treatment, female age, amount of gonadotropin used, treatment duration, peak estradiol level, and number of oocytes and embryos. RESULT(S): The women undergoing IVF after chemotherapy had poorer responses to gonadotropins than did the women with locally treated cancers even though they were younger (33.5 +/- 1.3 vs. 36.5 +/- 0.5 years; P<.05). The delivery rates after the women had undergone chemotherapy tended to be lower among the systemic treatment group than it was for the local cancer treatment group: (13.3% [2 of 15] vs. 40% [14 of 56, P=NS]). The women who had cryopreserved all embryos before chemotherapy produced more oocytes (18.7 +/- 3.2 vs. 14.5 +/- 1.2) and embryos (11.3 +/- 1.9 vs. 7.5 +/- 0.7) than did the women who had had a history of local cancer treatment. Male factor infertility as a result of cancer treatment is well treated with IVF or intracytoplasmic sperm injection, where indicated (32% delivery rate/cycle), with no difference between the frozen sperm banked before cancer treatment and fresh sperm produced after treatment. CONCLUSION(S): Chemotherapy diminishes the response to ovulation induction in assisted reproductive technologies. IVF with cryopreservation of embryos allows embryo banking before chemotherapy for women who have been newly diagnosed with cancer. Factors related to the partner affect the success of IVF for male factor infertility as a result of cancer treatment.     

Prolonged gonadotropin stimulation for assisted reproductive technology cycles is associated with decreased pregnancy rates for all women except for women with polycystic ovary syndrome

Purpose

To determine if etiology of infertility modifies the relationship between the duration of ovarian stimulation and success during assisted reproductive technology (ART) cycles.

Methods

A prospectively collected database was analyzed in an academic infertility practice. Eight hundred and twelve infertile women undergoing their initial fresh embryo, non-donor in vitro fertilization (IVF) or Intracytoplasmic Sperm Injection ICSI) cycle between January 1999 and December 2010 were evaluated. Clinical pregnancy was the main outcome measured.

Results

Out of 663 cycles resulting in oocyte retrieval, 299 produced a clinical pregnancy (45.1%). Women who achieved a clinical pregnancy had a significantly shorter stimulation length (11.9 vs. 12.1 days, p=0.047). Polycystic ovary syndrome (PCOS) was the only etiology of infertility that was significantly associated with a higher chance for clinical pregnancy and was a significant confounder for the association of duration and success of treatment. Women with 13 days or longer of stimulation had a 34 % lower chance of clinical pregnancy as compared to those who had a shorter cycle (OR 0.66, 95% CI:0.46-0.95) after adjustment for age, ovarian reserve, number of oocytes retrieved, embryos transferred and PCOS diagnosis.

Conclusion

Prolonged duration of stimulation is associated with decreased ART success for all couples, except for women with PCOS.