阴道微生态环境对辅助生殖技术安全性影响

尽管辅助生殖技术是当代治疗不孕症的核心技术,女性的生殖能力仍然主要取决于卵母细胞质量以及支持胚胎种植和发育的母体环境。阴道微生态环境是衡量女性生殖健康重要的评估指标,与不孕症及妊娠结局具有一定的相关性。在辅助生殖技术的实施过程中,阴道微生态环境随着控制性超促排卵、手术操作、内膜准备、妊娠状态等变化而改变,对助孕结局产生一定影响。重视阴道微生态环境,增强辅助生殖技术的安全性,为不孕症患者获得良好的助孕结局提供了新的思考方向。     

Prognosefaktoren der assistierten Reproduktion

Previous conceptions are one predictor for the outcome of assisted reproductive technology (ART) procedures. This study analyzes German IVF Registry data to examine the impact of former pregnancies on the outcome of ART procedures. The dataset consists of a total of 174,909 ART procedures performed between January 1998 and December 2000. Multiple logistic regression was used to assess the correlation between spouse/partner change, women’s age, and infertility diagnosis. More than one former pregnancy was negatively associated with ART regarding the woman’s age and duration of infertility. ART success was significantly more likely when a former pregnancy had been achieved through ART than when it was achieved by spontaneous conception. It was also demonstrated that any former miscarriage would increase the treatment-dependant miscarriage rate in ART procedures. A significantly higher impact was shown for one former miscarriage achieved by ART procedures compared to spontaneous conception. Partner change was shown to have no specific impact on the treatment-dependant pregnancy rate. A statistically significant increase of miscarriages in all ART procedures was found among women older than 34 years of age. The highest rate of treatment-dependant miscarriages was seen in ART procedures with cryopreserved embryo transfer. Successful ART procedures ending in a live birth or even a miscarriage predicted the success of subsequent ART procedures. More than one former pregnancy, age factors, and duration of infertility were inversely associated with ART success.     

Impact of laparoscopic cystectomy on fecundity of infertility patients with ovarian endometrioma

AIM: To clarify the effect of laparoscopic cystectomy for ovarian endometrioma in infertility patients, the pregnancy outcome was evaluated. METHODS: This was a retrospective study. From August 2002 to February 2006, 33 infertility patients with ovarian endometrioma underwent laparoscopic cystectomy at our center. According to the laparoscopic findings 33 were divided into two groups; 10 were evaluated as the patients who need assisted reproductive technologies (ART) treatment (IVF subgroup) and 23 were evaluated as the patients who do not need ART treatment but conventional infertility treatment (non-IVF subgroup). During the same period, 70 patients who were age-matched and received ART treatment without laparoscopy were defined as control (control group). Following up to 12 months after laparoscopy, the cumulative pregnancy rate in the non-IVF subgroup was calculated. RESULTS: The patients age, duration of infertility and size of endometrioma were equal in the IVF and the non-IVF subgroups. The revised-American Society of Reproductive Medicine (r-ASRM) score in the IVF subgroup was significantly higher than that in the non-IVF group (P < 0.05). The pregnancy rates after laparoscopic cystectomy in IVF and non-IVF subgroups were 50.0% and 60.9%, respectively. These rates in the IVF and the non-IVF groups were slightly higher than that in control group (41.4%), but these differences were not significant. The cumulative pregnancy rate in the non-IVF group reached 52.2%, 12 months after laparoscopic surgery. CONCLUSIONS: Laparoscopic surgery should be performed prior to ART treatment not only for making a decision about the treatment course but also for establishing a good pelvic condition to induce a pregnancy during ART treatment in infertility treatment with ovarian endometrioma.     

Ectopic pregnancy risk with assisted reproductive technology procedures

OBJECTIVE: To assess the ectopic pregnancy risk among women who conceived with assisted reproductive technology (ART) procedures. METHODS: The ectopic rate for ART pregnancies was calculated from population-based data of pregnancies conceived with ART in U.S. clinics in 1999-2001. Variation in ectopic risk by patient and ART treatment factors was assessed by using bivariate analyses and multivariable logistic regression. RESULTS: Of 94,118 ART pregnancies, 2,009 (2.1%) were ectopic. Variation was observed by procedure type. In comparison with the ectopic rate (2.2%) among pregnancies conceived with in vitro fertilization and transcervical transfer of freshly fertilized embryos from the patient's oocytes (fresh, nondonor IVF-ET), the ectopic rate was significantly increased when zygote intrafallopian transfer (ZIFT) was used (3.6%) and significantly decreased when donor oocytes were used (1.4%) or when a gestational surrogate carried the pregnancy (0.9%). Among fresh nondonor IVF-ET procedures, the risk for ectopic pregnancy was increased among women with tubal factor infertility (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.7-2.4; referent group = ART for male factor), endometriosis (OR 1.3, 95% CI 1.0-1.6), and other nontubal female factors of infertility (OR 1.4, 95% CI 1.2-1.6) and decreased among women with a previous live birth (OR 0.6, 95% CI 0.5-0.7). Transfer of embryos with an indication of high implantation potential was associated with a decreased ectopic risk when 2 or fewer embryos were transferred (OR 0.7, 95% CI 0.5-0.9), but not when 3 or more embryos were transferred. CONCLUSION: Ectopic risk among ART pregnancies varied according to ART procedure type, reproductive health characteristics of the woman carrying the pregnancy, and estimated embryo implantation potential. LEVEL OF EVIDENCE: II-2.     

Experience of pregnancy and delivery after ART

Differences in the experience of pregnancy and birth after ART compared to spontaneous conception are of interest for the developmental pyschologist. Studies performed to date have compared mainly the psychological aspects of experiencing the singleton pregnancy and the single birth. Couples after ART are at higher anxiety levels compared to those who have conceived naturally in the early stages of pregnancy. Individual experiences with infertility in those affected have often led to states of anxiety, low self-esteem and low confidence, but this does not seem to persist in pregnancy. Higher anxiety symptoms occur primarily. Increased symptoms of anxiety are found in pregnant women and their partners who have undergone the high stress of infertility. Pregnant women after ART are less concerned about the physical changes during pregnancy. Couples with previous ART mediated more harmony on the first impression, however, on the other hand being less communicative. A long duration of infertility (7 years or more) was associated with the expression of a large birth anxiety. Postpartum disorders such as depression are influenced by the interaction of several risk factors, particularly prematurity, multiple births and caesarean sections reinforce the emotional problems. Studies have confirmed an emotional well-being and a happy pregnancy with a satisfying mother-child relationship. However, where fears about the foetal surival are higher, postpartum difficulties are greater and self-esteem is lower after ART. Fears about the foetal survival and postnatal educational difficulties were greater after the application of assisted reproduction and the self-esteem lower. Pregnancy and parenthood after assisted reproduction may be idealised and is associated with a difficult transition to parenthood.     

The role and place of the assisted reproductive technology (ART) in treatment of infertility

The assisted reproductive technics (ART) compose the very valuable tool in the infertility treatment additionally to pharmacological and surgical methods. ART comparises the classical in vitro fertilization and embryotransfer (IVF/ET) intracytoplasmic sperm injection (ICSI) intrauterine insemination (IUI), microepididymal sperm spiration (MESA), and testicular sperm aspiration (TESA). Male infertility, tubal factor, ovarian factor, endometriosis or an unexplained infertility constitute pathologies where ART can be applied as the methods of choice or as the methods of the last chance. The efficacy of ART is closely related to the age of the female partner. Hence, taking a decision of the inappropriate treatment of the infertility and prolongation of such treatment for years is the "Theft" of the reproductive time of women and a diminution or even deprivation of the chance for pregnancy. The role and the appropriate time of the ART application in different infertility causes are described.     

辅助生殖妊娠并发子痫前期相关因素研究进展

子痫前期是严重影响母婴健康、造成母婴死亡的主要原因之一。辅助生殖技术(assisted reproductive technology,ART)是子痫前期的危险因素。随着不孕症患者逐年增多,通过辅助生殖治疗获得妊娠的比例不断增加,子痫前期发生率也随之增加。近年国内外研究发现子宫内膜异位症、多囊卵巢综合征、肥胖、多胚胎移植、冷冻胚胎移植、卵母细胞捐赠妊娠、着床期雌二醇峰值升高以及孕早期低浓度的人绒毛膜促性腺激素是子痫前期的危险因素,而孕激素是子痫前期的保护因素。这些因素单一或联合作用于子痫前期的发生发展。早期识别子痫前期危险因素、早期预防和早期干预是降低子痫前期发病率、改善母婴不良结局的关键。综述辅助生殖妊娠并发子痫前期的相关因素,为今后的辅助生殖妊娠围生期保健提供重要参考依据。     

A case of polycystic ovary syndrome conceived by intracytoplasmic sperm injection following laparoscopic ovarian drilling

Polycystic ovary syndrome (PCOS) is a disease in which an ovulation disorder is the main cause of infertility. Clomifene citrate (CC) is the treatment of first choice for ovulation induction in PCOS. If ovulation cannot be induced by CC, then either laparoscopic ovarian drilling (LOD) or gonadotropin therapy is selected as a subsequent treatment. Assisted reproductive technology (ART) is indicated for women with PCOS, similar to other infertility patients, when pregnancy is not achieved by intrauterine insemination (IUI). In this study, we experienced a case of PCOS in which pregnancy was achieved by ART following LOD. The case pertains to a 26-year-old patient. She consulted our hospital with a chief complaint of primary infertility. IUI with administration of CC plus recombinant follicle-stimulating hormone (rFSH) was carried out; however, pregnancy was not achieved. Subsequently, ART was carried out. In the first attempt, the development of several follicles was observed under the gonadotropin releasing hormone (GnRH) agonist long protocol. However, a fertilized oocyte was not obtained. In the second attempt, an ovum could not be collected after CC-rFSH ovarian stimulation. In the third attempt, a good quality embryo could not be obtained under the GnRH antagonist protocol, and therefore pregnancy could not be achieved. We performed LOD using a harmonic scalpel for the purpose of preventing severe OHSS and improving the quality of embryos. Following the operation, ovarian stimulation was performed under the CC-rFSH-antagonist protocol. Eighteen follicles were aspirated, six oocytes were picked-up, and five oocytes were normally fertilized. As a result, four embryos from day 2 culture were cryopreserved. Cryopreserved-thawed embryo transfer was thereafter performed, and a single pregnancy was achieved. LOD is a clinically effective treatment for PCOS requiring ART.     

Reproductive surgery vs assisted reproductive technologies: selecting the correct alternative

Many innovations have been made in advanced reproductive technologies (ART) over the past several years. These procedures now yield pregnancy rates of over 20% per cycle, rates that compare favorably to many types of reproductive surgery. Therefore, ART now represents a viable alternative for many patients suffering from infertility. As these pregnancy rates continue to rise, gynecologists will have to choose between ART and reproductive surgery for a larger number of patients. This article reviews the commonly performed reproductive surgical procedures and compares expected postoperative pregnancy rates to those of ART in order to help the gynecologist make this decision.     

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.     

Addressing the growing problem of multiple gestations created by assisted reproductive therapies

Iatrogenic multiple pregnancy is the most significant complication of assisted reproductive technology (ART). Approximately half of all children born subsequent to ART result from a plural gestation. Furthermore, the majority of triplets and higher order births are the product of ART. The risks for multiple pregnancy vary with practice patterns and the techniques used to achieve pregnancy. Recognizing the potential for serious morbidity associated with multiple pregnancies, infertility specialists have developed strategies to reduce the complication of multiple pregnancies while maintaining acceptable pregnancy rates. Implementation of these refined practices has led to a reduction in the incidence of higher order multiple births, although the incidence of twins has yet to be minimized. Further reduction in the incidence of multiple births after ART necessitates a redefinition of success to emphasize the healthy singleton birth rate, rather than crude pregnancy rates.     

Assessment and optimization of oocyte quality during assisted reproductive technology treatment

The health of fetuses, neonates, and adults depends on normal development of the oocytes and embryos from which they arise. In addition, the ability of an embryo to implant, sustain a pregnancy, and give rise to a viable offspring is unquestionably rooted in oogenesis. Therefore, defining markers that can reliably predict the best quality oocytes will prove invaluable in the care and management of infertility patients. Furthermore, identification of the best quality oocyte will also permit the transfer of a single embryo, thereby increasing overall pregnancy rates and reducing multiple rates. Although a few potentially important predictors of oocyte quality have been identified, their application for routine use in the assisted reproductive technology (ART) laboratory remains to be established. With the critical need for markers to be noninvasive, reliable, and assayable with a rapid turnaround, key areas that will take advantage of recent technological advances are identified in this article. Oocyte quality also needs to be improved in the management of human infertility by ART programs. Given that mechanisms determining oocyte quality are multifactorial and complex, several possible areas that continue to necessitate optimization are discussed.     

Sexualité et infertilité

Following the recent medical innovations, it is now possible to disassociate sexuality and reproduction. With contraception, people can have free sexuality without the fear of an unexpected pregnancy. Frequently, Assisted Reproductive Technologies (ART), with in vitro fertilization, can obtain a pregnancy without intercourse. There are three major problems concerning infertility and sexuality. Firstly, infertility because of a sexual disorder; secondly, sexual disorder induced by infertility diagnosis; thirdly, sexual disorder induced by ART. Praticians should be aware of possible existence of sexual problems to allow the couple to express them. Once diagnosed, these troubles can be treated by the pratician himself or the couple has to be referred to a psychologist or a sexologist.     

Endometriosis and assisted reproductive technologies.

The association between endometriosis and infertility is well established, and different mechanisms have been postulated to cause infertility depending on the stage of endometriosis. Controlled ovarian hyperstimulation improves pregnancy outcome for minimal to mild endometriosis; however, there are no randomized controlled studies of this technique in patients with severe disease. Further, ART appears to have an overall beneficial effect for all stages of endometriosis. Based on the current staging system, several studies have not been able to demonstrate a significant difference in true outcomes for different stages of the disease. The limitations of these studies have been discussed above. Similarly, the effect of endometriomas when considered independent of the stage is still unclear. In addition to ART, pretreatment with GnRH analogues or surgical intervention may be beneficial and needs to be addressed in randomized controlled studies. It is evident that we urgently need large randomized studies to answer several questions about the treatment of endometriosis-associated infertility with ART. Although our current practice is based primarily on retrospective observational studies and small randomized studies, the overall impact on pregnancy outcome is beneficial.     

Are children born after assisted reproductive technology at increased risk for adverse health outcomes?

As assisted reproductive technologies (ARTs) are increasingly used to overcome infertility, there is concern about the health of the children conceived. The empirical evidence for associations with outcomes related to child health is variable and should be evaluated with consideration of methodological shortcomings. Currently, there is convincing evidence that ART treatment may increase the risk of a few outcomes. Experimental laboratory studies document that various constituents in culture media affect various embryo characteristics both positively and negatively. Multiple-gestation pregnancy and birth are increased with ART, both because of multiple embryo transfer and embryo splitting. There is evidence of an increase in chromosomal abnormalities among pregnancies conceived using intracytoplasmic sperm injection and low birth weight and preterm delivery among singletons conceived with all types of ART; however, there remains uncertainty about whether these risks stem from the treatment or the parental infertility. For some outcomes, data of an increased risk with ART are suggestive at best largely because of lack of purposeful study of sufficient size and scope. These include specific perinatal morbidities, birth defects, developmental disabilities, and retinoblastoma. The evidence for an association between ART and spontaneous abortion is inconsistent and weak. There is inconclusive evidence that ART may be associated with genetic imprinting disorders. For childhood cancer, chronic conditions, learning and behavioral disorders, and reproductive effects there is insufficient empirical research to date, but given the data for more proximal outcomes, these outcomes merit further study. Future research needs to address the unique methodological challenges underlying study in this area.     

子宫腺肌病合并不孕患者的生殖预后及助孕策略

在子宫结构异常疾病中，子宫腺肌病在育龄妇女中有较高的发病率。随着影像技术和治疗水平的提高，越来越多的研究表明子宫腺肌病可能影响育龄妇女的生育能力。子宫腺肌病合并不孕的机制尚不明确，子宫内膜容受性异常、子宫结合带的结构异常、免疫功能异常等可能是子宫腺肌病患者生育能力低下的原因。希望保留生育能力的主要治疗方案有药物治疗、辅助生殖技术（ART）和手术切除子宫腺肌病灶。目前，ART可以改善子宫腺肌病合并不孕症患者的妊娠结局，促性腺激素释放激素类似物对生殖有积极的影响，在子宫腺肌病合并不孕症应用中有很重要的价值。综述子宫腺肌病合并不孕症影响生育的可能机制、生殖结局及治疗策略以探讨子宫腺肌病与不孕的关系。     

Tratamiento conservador del cáncer de endometrio en una pareja estéril

Successful conservative management for early-stage low-grade endometrial cancer in young women wishing to preserve fertility has been reported in small series. Although few data are available on assisted reproductive technology (ART) outcomes after conservative management of endometrial carcinoma, ART does not seem to worsen prognosis. We report the case of a 29-year-old woman with a history of primary infertility, who was diagnosed with a well-differentiated endometrial adenocarcinoma (stage Ia), which was treated with high doses of oral progesterone. A successful pregnancy was achieved after ART.     

The occurrence of ectopic pregnancy with and without clomiphene citrate use in assisted and nonassisted reproductive technology

An eleven-year review of treatment records of patients who became pregnant as a result of infertility treatment (n=3692) was conducted. All records were examined to determine whether clomiphene citrate (CC) was used in the cycle of conception and whether or not an ectopic pregnancy occurred. Data were additionally analyzed for the incidence of ectopic pregnancy with and without assisted reproductive technology (ART). The incidence of ectopic pregnancy was similar between CC (3.4%) and non-CC (3.4%) treatment groups receiving non-ART treatment. For non-ART treatments, tubal disease and severe endometriosis resulted in an increase in ectopic pregnancies independent of CC use. The incidence of ectopic pregnancy in patients receiving CC + human menopausal gonadotropin (hMG) for in vitro fertillization (5.4%) and gamete intrafallopian transfer (3.1%) was similar compared to ART treatments with hMG alone. The incidence of ectopic pregnancy was more closely associated with infertility diagnosis rather than CC use.Presented in part at the Annual Meeting of the Pacific Coast Fertility Society in Palm Springs, California, April 12, 1989.     

The value of treatment for infertility: A systematic literature review of willingness-to-pay thresholds and approaches for determining the cost effectiveness of fertility therapies

Willingness to pay (WTP) for an infertility treatment is the maximum amount of money a patient is willing to pay per treatment, or to achieve a live birth or pregnancy. Such thresholds are important to determine the cost effectiveness of a treatment. A systematic review was conducted to identify and explore the studies that attempt to ascertain WTP for infertility and compare them with the cost-effectiveness studies that claimed to use WTP thresholds. For comparison, all the costs were converted and inflated to 2021 euros. The results demonstrated that there were no standard outcomes or WTP thresholds for an outcome/treatment, and the methodologies used vary. Cost-effectiveness studies either used the incremental cost-effectiveness ratio to imply a WTP threshold, or used thresholds that were previously accepted for a quality-adjusted life year outcome converted, inappropriately, to an infertility outcome. There is a need for further research by health economists to develop a consensus for the meaningful assessment of WTP for ART.     

Adipositas und assistierte Reproduktion

Obesity takes on a significant role in reproductive medicine: associated with PCOS it constitutes a frequent reason for infertility, and on the other hand it influences nature and outcome of assisted reproductive technologies (ART), a relation that should be considered when consulting and treating obese infertility patients. Obese patients appear to be at a disadvantage in ART programs by a series of possible negative events: inefficient ovarian stimulation, reduced quantity and quality of oocytes and transferred embryos, decreased pregnancy rates, increased abortion rates, and a lower live birth rate. Obese patients therefore should lose weight prior to infertility treatment and prior to conception; the reproductive endocrinologist could possibly initiate adequate measures.