Reproductive Outcomes after Fertility-Sparing Surgery for Focal and Diffuse Adenomyosis: A Systematic Review

Among the variety of treatment options to improve reproductive outcomes for infertile women with adenomyosis (AD), uterine-conserving surgery has shown varying success. Hence, we conducted a systematic review around the topic of fertility-sparing surgery across 18 studies and 1396 infertile women with focal and diffuse AD. Patients with focal AD showed mean pregnancy and miscarriage rates of 52.7% (range,14.3%–77.5%) and 21.1% (range, 0%–44.4%), respectively, whereas patients with diffuse AD had mean pregnancy and miscarriage rates of 34.1% (range, 9.4%–100%) and 21.7% (range, 12.5%–33.3%), respectively. Uterine rupture and preterm birth were observed in 6.8% (3/44) and 4.5% (2/44) of pregnant patients with diffuse AD versus 0% (0/35) and 10.9% (12/110) of patients with focal AD, respectively. No significant differences were observed between natural conception versus assisted reproductive technology (ART) with or without gonadotropin-releasing hormone agonist pretreatment. Overall, patients with focal AD appeared to have higher pregnancy rates after conservative surgery compared with diffuse AD, whereas a higher incidence of uterine rupture was reported after surgery for diffuse AD. However, significant heterogeneity precludes any direct comparison, and prospective controlled trials are required to further elucidate the benefits of fertility-preserving surgery over medical or expectant management for AD-related infertility. In view of the debatable benefits of conservative surgery and the possible increase in adverse pregnancy outcomes, particularly in cases of diffuse AD, clinicians should consider surgery on a case-by-case basis because it may be appropriate for women with concurrent AD-associated pelvic pain or menorrhagia, younger infertile women who have failed medical management or older women with infertility despite ART, and those with a history of recurrent pregnancy loss or implantation failure.     

Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis

OBJECTIVE: To examine whether ultralong GnRH analog (GnRH-a) therapy after surgical treatment of endometriosis and before ART influences the pregnancy rate. DESIGN: Prospective, randomized, controlled study. SETTING: University clinic for reproductive medicine and gynecologic endocrinology. PATIENT(S): One hundred ten patients with stage II to IV endometriosis according to ASRM criteria. INTERVENTION(S): Fifty-five patients received GnRH-a for 6 months after surgery and subsequently underwent up to 3 cycles of ART, and 55 patients received 3 cycles of ART alone immediately after surgery. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULTS: The pregnancy rate per patient was higher among patients who received follow-up treatment with GnRH-a. The same results were found in patients with stage III or IV endometriosis who were undergoing IUI or IVF/ICSI. CONCLUSION(S): Ultralong GnRH-a therapy increases the pregnancy rate of ART in patients with severe endometriosis.     

What are the risks of the assisted reproductive technologies (ART) and how can they be minimized?

Although assisted reproductive technologies (ART) have become established procedures performed around the world, there are still many unanswered questions regarding safety. Possible risks associated with infertility and ART include (1) those inherent to pregnancy, delivery, and childhood; (2) those associated with the infertility itself and its causes; and (3) risks iatrogenic to ART. Although there are many potential risks associated with ART, it has become clear that the major risk is multiple pregnancy and its consequences. Major efforts are warranted to reduce the risk of multiple gestations with IVF, but it is also clear that single-embryo transfer is not the solution in all cases. Moreover, several studies have now documented that perinatal outcomes are somewhat poorer in IVF singleton infants than in spontaneously conceived singletons, but it is not clear if this increased risk is due to the ART or the infertility. Concerns about the impact of abnormalities in genomic imprinting persist at this time, as do risks associated with the culture conditions and even our environment. Only time will tell if children born following ART are at any increased risk of developing certain chronic diseases as they age. In any case, the risks to IVF children and mothers are likely to remain higher than those for children and mothers conceived spontaneously without medical assistance. However, since there have been over 5 million births after ART worldwide, and the vast majority of pregnancies and children have been essentially “normal”, it is obvious that any excess risk must be relatively small. The normality of most pregnancies mandates that extreme care be exercised in making any changes to current practice.     

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.     

Impact of reproductive history on in vitro fertilization and intracytoplasmic sperm injection outcome: evidence from the German IVF Registry

OBJECTIVE: To evaluate the effect of reproductive history on the outcome of different procedures in assisted reproductive technologies (ART) comparing IVF, ICSI, and cryopreserved embryo transfer (CPE). DESIGN: Prospective registration of ART cycles and their outcomes. SETTING: One hundred three reproductive programs in Germany. PATIENT(S): Women undergoing 174,909 ART procedures from January 1998 through December 2000. INTERVENTION(S): Data analysis of reproductive history collected by the German IVF Registry; multiple logistic regression modeling of success rates. MAIN OUTCOME MEASURE(S): Effect of type of conception and outcome of previous pregnancies, duration of infertility, female's age, and type of ART on clinical pregnancy rate per retrieval. Odds ratios with 95% CIs are reported. RESULT(S): More than one previous pregnancy was negatively correlated with outcome of IVF, ICSI, or CPE. This association disappeared when female age was restricted to a maximum of 35 years. A previous pregnancy achieved by spontaneous conception had less impact on outcome of IVF, ICSI or CPE outcome than did a previous assisted conception. Previous live births and miscarriages demonstrated a statistically significant increase compared with ectopic pregnancies and induced abortions. CONCLUSION(S): Reproductive history must be considered when counseling subfertile couples. Female age, method of conception, and previous pregnancy outcome have a significant effect on IVF, ICSI, and CPE outcome.     

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.     

Laparoscopy should be strongly considered for women with unexplained infertility

AIM: Women with unexplained infertility frequently become pregnant after diagnostic laparoscopy. In this study the effect of laparoscopic surgery on such women was evaluated by the pregnancy rate after laparoscopic surgery. METHODS: A total of 47 unexplained infertile women underwent laparoscopic evaluation during the period August 2002 to January 2005 in our center. The percentage of positive laparoscopic findings and the pregnancy rate after laparoscopy were calculated. The patients were divided into 5 subgroups according to maternal age, pregnancy rates were calculated for each group, and compared with the outcome of assisted reproductive technology (ART) treatment for the same age groups. RESULTS: In 87.2% of the women, laparoscopy revealed abnormal findings; endometriosis lesions, peritubal adhesions and tubal obstructions were found in 21, 17 and 3 cases, respectively. After laparoscopy 23 achieved pregnancy (pregnancy rate: 48.9%). The pregnancy rates of the groups at the age of 25 years old or less, 26-30, 31-35, 36-40 and over 41 years old were 100%, 75.0%, 45.5%, 27.2% and 0%, respectively. In the case of the 26-30 years old group, the pregnancy rate after laparoscopy was significantly higher than that in the ART treatment group (33.3%, P < 0.05). CONCLUSIONS: Laparoscopy should be strongly considered for examining women with unexplained infertility.     

Invasive procedures in multiple gestations

PURPOSE OF REVIEW: The incidence of multiple gestations has increased significantly with advances in assisted reproductive techniques resulting in a concomitant increase in invasive procedures in these pregnancies. Commonly performed invasive procedures include amniocentesis, chorionic villus sampling, multifetal pregnancy reduction, and selective termination. Amniocentesis and chorionic villus sampling are also performed in singleton pregnancies, while multifetal pregnancy reduction and selective termination are procedures that are unique to multiple gestations. RECENT FINDINGS: With increased operator experience, pregnancy loss rates after chorionic villus sampling, multifetal pregnancy reduction, and selective termination have decreased to acceptably low levels. Amniocentesis and chorionic villus sampling continue to have similar loss rates in experienced hands. A recent study suggests that amniocentesis in twins may have a higher post-procedural loss rate than in singletons; this may be due to the higher background loss rate of twins. There has been a recent increase in multifetal pregnancy reduction to a singleton with a trend towards improved outcomes over reduction to twins; future studies should focus on whether this confers a definitive advantage. Newer data suggests that selective termination after 20 weeks gestation in experienced hands does not increase loss rates over those procedures performed before 20 weeks. Newer techniques, such as cord coagulation, continue to be developed for selective termination in monochorionic pregnancies, though still with considerable morbidity and mortality. SUMMARY: In summary, invasive procedures in multiple gestations are now commonly performed with. It is our hope that primary prevention of high order multiple pregnancies by optimization of assisted reproductive techniques will decrease the need for these procedures.     

Hysteroscopic Resection of Endometrial Polyps and Assisted Reproductive Technology Pregnancy Outcomes Compared with No Treatment: A Systematic Review

Endometrial polyps are frequently encountered in the uterine cavity of infertile women. There is much debate regarding the treatment of endometrial polyps in patients who are undergoing assisted reproductive technology (ART). A systematic review was performed by searching PubMed, Embase, and the Cochrane Library for retrospective or prospective studies that compared the effect of hysteroscopic resection of polyps with no treatment on pregnancy outcomes of patients who underwent ART. The primary outcomes were clinical pregnancy, live birth, miscarriage, and implantation rates after ART. Eight studies with a total of 2267 patients were included. The results showed that hysteroscopic resection of endometrial polyps (mean size <2 cm) was associated with an increased rate of clinical pregnancy in patients who underwent intrauterine insemination. No clear benefit was observed for clinical pregnancy, live birth, miscarriage, or implantation rates in patients who underwent in vitro fertilization/intracytoplasmic sperm injection cycles. In conclusion, the effect of hysteroscopic polypectomy on pregnancy outcomes of patients who have undergone ART remains unclear. More prospective, randomized controlled trials are warranted to determine appropriate treatment.     

辅助生殖技术与多胎妊娠的关系及减胎术

辅助生殖技术(又称助孕技术)的发展在治疗不孕的同时导致多胎妊娠率的提高。本文阐述助孕技术与多胎妊娠的关系,以及如何通过严格控制超促排卵指征、控制移植胚胎数量、冻存胚胎、选择性单胚胎移植、减胎术的应用等方法来获得最佳妊娠率,同时降低助孕术后的多胎妊娠特别是三胎及三胎以上妊娠的发生。     

Effectiveness of postoperative adjuvant therapy in improving reproductive outcome of endometriosis-associated infertility.

BACKGROUND AND PURPOSE: Treatment of endometriosis-associated infertility has not yet become standardized. Various protocols including surgical treatment, medical therapy, and a combination of both have been suggested but their use remains controversial. The objective of the present study was to determine whether postoperative adjuvant therapy for endometriosis is effective in improving reproductive outcome. METHODS: Medical records of infertile patients with newly diagnosed endometriosis treated in a university teaching hospital during a 50-month period were reviewed. After exclusion of patients with other major infertility factors, a total of 209 patients were included in the retrospective analysis. These patients were divided into those receiving (n = 78) or not receiving (n = 131) peri- or postoperative adjuvant medical therapy. The adjuvant therapies included danazol (n = 62), gonadotropin releasing hormone analogues (n = 11), progestins (n = 3), oral contraceptives (n = 1), and mixed treatment (n = 1). RESULTS: The pregnancy rate was lower in those receiving adjuvant therapy, although this result was not significant (32.1% vs 45.8%; p = 0.05). When patients using postoperative danazol therapy were considered alone, the pregnancy rate in patients receiving adjuvant therapy was significantly lower than that in patients not receiving it (p = 0.047). When the stage of endometriosis was considered, the pregnancy rate in patients receiving adjuvant therapy was again lower than in those not receiving it in patients with minimal or mild endometriosis (42.9% vs 60%; p = 0.043). However, in patients with moderate or severe endometriosis, the pregnancy rate was not different in the two groups (31% vs 36%; p = 0.56). Postoperative assisted reproductive techniques (ART) including controlled ovarian hyperstimulation/intrauterine insemination (COH/IUI) and in vitro fertilization (IVF) were effective in improving the pregnancy rates for all patients (53.9% with ART vs 33.1% without; p = 0.003) and for patients with advanced endometriosis (47.7% with ART vs 27.2% without; p = 0.016). CONCLUSIONS: Our results suggest that postoperative adjuvant therapy is ineffective in improving reproductive outcome in patients with either early (minimal or mild) or advanced (moderate and severe) endometriosis. This finding suggests that if fertility is the goal of treatment, adjuvant therapy may be unnecessary after surgery. In contrast, our data suggest that empirical ART, including COH/IUI or IVF, may be a better alternative to improve the pregnancy outcome after surgery.     

Endometriosis and infertility

Endometriosis seems to be a common fertility barrier which is affected by immunological and local mechanical factors. The established use of assisted reproductive technologies (ART) provides increasing knowledge about folliculogenesis, fertilization, embryo development and pregnancy rates. Nevertheless, controversial discussion about the success of ART in endometriosis exists although the progress of reproductive technologies is improving constantly in many ways. Despite all discussions the question remains still to be unanswered, whether or not endometriosis is indeed limiting the success in reproductive medicine.     

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.     

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.     

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.     

Surgical intervention in infertility management

Despite improvement in the success of IVF, reproductive surgery will remain an important option and complement to assisted reproductive technologies (ART) for many couples. Reproductive surgery should be considered as the first-line treatment when the correction of infertility pathologies is simple and a good result is expected once corrected, when the pathology is causing symptoms such as pain or abnormal bleeding, or if uncorrected will compromise the results or increase the risks of ART. The success of surgical infertility treatment depends on the careful selection of cases using appropriate investigative techniques, with procedures performed in centres with sufficient expertise. For both specialized reproductive and general gynaecological surgery it is crucial to follow microsurgical principles to avoid adhesion formation and conserve normal tissues, especially tubal and ovarian. These aspects of reproductive surgery, and different surgical techniques used for various tubal, peritoneal, uterine and ovarian conditions to achieve the optimal reproductive outcome are discussed in this article.     

Consequences of superovulation and ART procedures

Superovulation procedures and assisted reproductive technologies (ART) have provided the means for significant improvement in infertility care. Although generally safe, these procedures are associated with complications that, albeit rare, can have significant morbidity. Complications from superovulation include ovarian hyperstimulation syndrome, thromboembolism, and adnexal torsion. Complications from oocyte retrieval include infection, bleeding, bowel injury, and anesthetic complications. Early pregnancy complications from in vitro fertilization include multiple gestations, ectopic pregnancy, and heterotopic pregnancy. Stimulation, retrieval, and transfer techniques can be modified to minimize these risks and prevent complications. Further research in the field is needed to continue to improve the safety of superovulation and ART.     

Laser technology in the ART laboratory: a narrative review

To improve success rates, assisted reproductive technology (ART) procedures continually undergo optimization and enhancement such that the best quality gametes and embryos can be identified and manipulated, thus improving clinical outcomes. Laser technology is now being applied across ART to reduce procedure times and increase the consistency and reproducibility of traditional ART techniques such as assisted hatching, embryo biopsy, intracytoplasmic sperm injection cryopreservation and sperm immobilization/selection. This review examines the current status of cutting-edge laser-assisted reproductive technologies, investigates experimental techniques that are increasingly being applied clinically. It highlights the benefits of lasers as a powerful technology at the forefront of both diagnostic and therapeutic treatments for general subfertility and male-factor infertility. However, it is important to note that although lasers are becoming increasingly commonplace in ART units, there is comparatively little information in the existing literature pertaining to the potential negative effects that laser application might have on the developing human embryo, thus creating the need for further investigative research.     

Hydrosalpinx – Salpingostomy,salpingectomy or tubal occlusion

Tubal factors account for approximately 25% of cases of infertility, and the most severe manifestation of tubal disease is hydrosalpinx, accounting for 10–30% of tubal diseases. Hydrosalpinx is a distension or dilatation of the fallopian tube in the presence of a distal tubal occlusion, and the most common cause is pelvic inflammatory disease. Women with hydrosalpinges have lower implantation and pregnancy rates in assisted reproductive technology (ART), due to a combination of mechanical and chemical factors thought to disrupt the endometrial environment. Current guidance is removal of the tube by salpingectomy (preferably laparoscopically) before IVF treatment. Salpingostomy, or distal tubal plastic surgery in the management of hydrosalpinx, is an alternative for women desiring natural conception, although ectopic pregnancy rates as high as 10% have been reported. Proximal tubal occlusion with Essure^® devices placed hysteroscopically can be considered particularly in cases of distorted pelvic anatomy or pelvic adhesions making abdominal surgery complex. However, low clinical pregnancy and live birth rates have been reported with the use of these devices before IVF. In this review, we discuss salpingostomy, salpingectomy and tubal occlusion as possible management options for the reproductive women with hydrosalpinx.     

Comparison of implantation and pregnancy rates in African American and white women in an assisted reproductive technology practice.

OBJECTIVE: To compare IVF outcomes between infertile African American and white women. DESIGN: Retrospective cohort study. SETTING: Hospital-based IVF practice. PATIENT(S): Women undergoing IVF procedures between November 1996 and June 2000. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation and pregnancy rates. RESULT(S): There were 24 African American and 273 white women < or =40 years of age who underwent 25 and 333 IVF cycles, respectively. African American women were more likely to have had tubal factor as a primary diagnosis, to have had a child, and to have undergone fewer previous assisted reproductive technology (ART) cycles as compared to white women. No differences between the two groups for clinical variables were noted with the exception of body mass index (BMI [kg/m(2)], 27.1 in African Americans vs. 24.8 in whites). Implantation rates were higher in African American than in white women (35% vs. 23%, respectively). Pregnancy rates were 71% in African Americans and 48% in whites. After adjustment for tubal factor, BMI, and parity, the odds ratio for pregnancy in African American women versus white women increased from 2.6 to 3.3. CONCLUSION(S): This is the first study to demonstrate a significantly higher clinical pregnancy rate in African American women as compared to white women undergoing ART. These data strongly contradict a recent study comparing the same two groups of women undergoing ART. We urge other ART centers to report their data pertaining to race.