Heterotopic pregnancy following in vitro fertilization and embryo transfer: 12 cases report

Objective  To evaluate the incidence, predisposing factors, early diagnosis and treatment options of heterotopic pregnancy (HP) following in vitro fertilization and embryo transfer (IVF-ET) procedure. Methods  A retrospective review study was performed to identify the HP cases after IVF-ET at the Reproductive Centre in Guangdong Women and Children’s Hospital in China between the years of 2002–2007. Results  Twelve out of 1,476 pregnancies (0.81%) were diagnosed for HP, of which nine patients elected for exploratory salpingectomy, two patients received selective fetal reduction by embryo aspiration under ultrasound guidance, and one patient opted for expectant treatment. Postoperatively, four intrauterine pregnancies were continued to develop until term while two were delivered at 35 weeks of gestation. The achievement ratio of continuous pregnancy was 66.7% (6/9). Conclusion  The incidence of HP is increasing due to the widespread use of assisted reproductive technology. An early transvaginal sonography performed by experienced radiologist/radiographer is considered to be essential and beneficial in establishing early diagnosis of HP. Both salpingectomy and selective fetal reduction by embryo aspiration can be administered as one of the effective therapies for HP with the optimal outcome of intrauterine pregnancy.     

Prognostic value of serum progesterone and LH values on the day of hCG administration in IUI GnRH antagonist cycles

Objetive: to evaluate the effect of LH surge and progesterone rise in IUI cycles under gonadotropin stimulation with GnRH antagonist coadministration on pregnancy rates (PR). Study Design: The population under study consisted of 152 women prospectively studied and subjected to IUI. Results The higher the progesterone cutoff value, the lower the PR were 26.5% and 10.9% when the cutoff was 1 ng/mL, 26.0% and 8.6% when the cutoff was 1.2 ng/mL, 25.6% and 7.1% when the cutoff was 1.4 ng/mL and 25.3% and 0% when the cutoff was 1.6 ng/mL. Conclusion: In IUI cycles under GnRH antagonist coadministration, serum progesterone levels over 1.0 ng/mL are associated with lower PR, the higher the progesterone levels, the lower the PR.     

Oral melatonin supplementation improves oocyte and embryo quality in women undergoing in vitro fertilization-embryo transfer

The aim of this study was to evaluate the efficacy of oral melatonin supplementation on oocyte and embryo quality in patients in an assisted reproductive technologies program. All patients were treated for at least 2 weeks with melatonin (3?mg/day). To evaluate the cumulative effect of melatonin supplementation, we compared cycle outcomes between the first (no supplementation) and second cycles (melatonin supplementation) of patients who completed two treatment cycles. There were no significant differences in maturation rates (p?=?0.50), blastocyst rates (p?=?0.75), and the rate of good quality blastocysts (p?=?0.59) between the first and second cycles. The fertilization rate of ICSI was higher in the second cycle than that in the first cycle (69.3 versus 77.5%). Being limited to patients with a low fertilization rate in the first cycle (<60%), the fertilization rate dramatically increased after melatonin treatment (35.1 versus 68.2%). The rate of good quality embryos also increased (48.0 versus 65.6%). An important finding in our study was that oral melatonin supplementation can have a beneficial effect on the improvement of fertilization and embryo quality and this may have occurred due to a reduction in oxidative damage.     

Relationship between the day of embryo transfer and the outcome in human in vitro fertilization and embryo transfer

Purpose To clarify the optimal date of embryo transfer (ET), we retrospectively analyzed the relationship between the day of ET and the outcome in human in vitro fertilization and embryo transfer (IVF-ET).Method Of a total of 307 human IVF-ET cycles performed at Kyoto University Hospital between January 1990 and March 1994, we focused on 207 cases of IVF-ET cycles in which two or three good-quality embryos were transferred. These 207 IVF-ET cycles consisted of 54 Day 2 ET cycles, 79 Day 3 ET cycles, 46 Day 4 ET cycles, and 28 Day 5 ET cycles. We compared the pregnancy and live-birth (plus ongoing pregnancy) rates among these four ET groups.Results The pregnancy rates of ET on Days 2 to 4 were not significantly different, whereas Day 5 ET produced a significantly lower pregnancy rate (Day 2, 29.6%; Day 3, 32.9%; Day 4, 30.4%; Day 5, 10.7%). Similar results were obtained for the live-birth (plus ongoing pregnancy) rates (Day 2, 20.3%; Day 3, 18.9%; Day 4, 17.9%; Day 5, 7.1%).Conclusions These results suggest that the day of ET does not fundamentally affect the pregnancy rate in human IVF-ET provided that transfer is made before Day 5.     

Very early pregnancy wastage in in vitro fertilization and embryo transfer (IVF-ET)

The occurrence and incidence of early pregnancy wastage in an in vitro fertilization and embryo transfer (IVF-ET) program have been studied in 750 patients. In 297 (39.6%) a pregnancy was diagnosed; of these, 14.8% were biochemical and 24.8%, clinical pregnancies. In the latter group 23.6% aborted, while 75.8% had clinical ongoing pregnancies. The mean embryo quality score of the biochemical pregnancy group was similar to that of the clinical ongoing pregnancy group but statistically different from that of the clinical abortion group (P<0.005). Furthermore, the clinical ongoing pregnancy rate in women with previous biochemical pregnancy was 24.7%, a significantly higher percentage compared to clinical ongoing pregnancies achieved in IVF-ET cycles (P<0.05). It is possible that biochemical pregnancy does not represent an index for infertility but rather an intact stage of reproduction leading toward implantation. The high clinical pregnancy rate in subsequent cycles may probably serve as an encouraging sign or a marker for future clinical pregnancy.     

Placental development during early pregnancy: Effects of embryo origin on expression of chemokine ligand twelve (CXCL12)

The aim was to localize chemokine ligand twelve (CXCL12) in sheep placental tissues during early gestation and after assisted reproductive technologies (ART). Uteri were collected from naturally (NAT) mated ewes and ewes receiving embryo transfer (ET), in vitro fertilization (IVF) or in vitro activation (IVA). CXCL12 was immunolocalized to endometrial stroma, glands, and trophoblast. Greater CXCL12 immunoreactivity was present in trophoblast on day 22 and 24 and in NAT ewes compared to IVF and IVA. Increased CXCL12 expression suggests CXCL12 promotes implantation and placentation. Decreased CXCL12 in IVF and IVA embryos, may compromise pregnancy establishment when utilizing ART methods.     

Expectations for oocyte fertilization and embryo cleavage after whole sperm versus sperm head intracytoplasmic sperm injection

OBJECTIVE: To compare oocyte fertilization and embryo development after intracytoplasmic sperm injection (ICSI) with a whole sperm vs. a sperm head. DESIGN: Retrospective study. SETTING: Hospital-based IVF practice. PATIENT(S): Fifty-three women undergoing 54 IVF-embryo transfer plus ICSI procedures between January 1999 and June 2002. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Oocyte fertilization, zygote cleavage, and embryo stage after 72 hours of culture. RESULT(S): A significantly higher fertilization rate was observed using whole sperm (72.2%) than when using sperm heads (56.4%). Zygote cleavage rates for whole sperm vs. sperm head ICSI were 96.4% and 92.7%, respectively. Embryo cell stage after 72 hours of culture for whole sperm vs. sperm head ICSI was 6.5 +/- 2.1 cells and 5.6 +/- 1.8 cells, respectively. Embryo grade at this same time point was not different (2.3 +/- 1.0 and 2.5 +/- 0.9, respectively). CONCLUSION(S): The ICSI using whole sperm produces superior fertilization rates compared to ICSI using sperm heads, but once oocytes were fertilized, zygote cleavage rates were not different between the two sperm sources. Oocytes injected with a whole sperm produced embryos of higher cell stage but equivalent quality compared to oocytes injected with sperm heads. Therefore, having only sperm heads for use in ICSI should not be a deterrent to using this procedure.     

Influence of embryo transfer depth on in vitro fertilization and embryo transfer outcomes

OBJECTIVE: To investigate the influence of transfer distance from the fundus (TDF) on clinical pregnancy rate (PR) and ectopic pregnancy rate. DESIGN: Retrospective cohort. Between January 2000 and December 2001, 699 ultrasound (US)-guided embryo transfers were conducted. Mock transfer was performed to measure uterine cavity depth 1 month before treatment. Cavity depth was measured by abdominal US before the transfer, from the vaginal stripe to the fundus. Transfers were performed with a Wallace embryo transfer catheter (Cooper Surgical, Shelton, CT) using US and physician's judgment of cavity depth. Transfer distance from the fundus was calculated by subtracting the depth of catheter insertion from the cavity depth, as determined by US or by mock transfer. Statistical analyses were performed by building a multivariable logistic regression model to calculate odds ratios and 95% confidence intervals (CI). SETTING: Women aged 23 to 43 years who are in a university-affiliated, community-based IVF program in Springfield, Massachusetts. PATIENT(S): All patients enrolled in IVF program undergoing embryo transfer. INTERVENTION(S): No patient received any additional procedure or intervention. All of the measurements obtained with the embryo catheter and the transvaginal ultrasound were part of the program's protocol for the embryo transfer. MAIN OUTCOME MEASURE(S): Odds ratio examining relationship between embryo transfer depth and PR.Clinical, implantation, and ectopic PR were 37%, 20%, and 2.1%. Cavity depth by US differed from cavity depth by mock by at least 10 mm in >30% of cases. The TDF by US was highly predictive of PR; TDF by mock was not predictive of PR. Increasing the TDF by US resulted in significantly increased PR as well as lower ectopic rates. Using regression analysis, the odds ratio for TDF by US was 1.11 (95% CI: 1.07-1.14). This suggests that for every additional millimeter embryos are deposited away from the fundus, the odds of clinical pregnancy increased by 11%. CONCLUSION(S): After controlling for potential confounders, the clinical PR is significantly influenced by the transfer distance from the fundus. Cavity depth by US is clinically useful to determine the depth beyond which catheter insertion should not occur.     

Effect of progesterone supplementation in early pregnancy on the pregnancy outcome after in vitro fertilization

A retrospective cohort study was performed to evaluate IVF clinical pregnancy rates and livebirth rates between patients receiving progesterone supplementation through the first trimester of pregnancy (first trimester protocol) at 12 weeks vs. discontinuation after a positive beta-hCG test 2 weeks after retrieval (luteal protocol) at 4 weeks of pregnancy. A similar rate of clinical pregnancies occurred at 7 weeks (81.8% luteal protocol vs. 85.8% first trimester protocol; P=.49) and for livebirth rates (76.8% luteal protocol vs. 75.0% first trimester protocol; P=.80), but a trend toward a higher rate of pregnancy loss after 7 weeks in the first trimester protocol group occurred (15.5% vs. 4.4%; P=.06), indicating that first trimester progesterone supplementation may support early pregnancy through 7 weeks by delaying miscarriage but does not improve livebirth rates.     

Multiple attempts at embryo transfer: Effect on pregnancy outcome in an in vitro fertilization and embryo transfer program

Purpose This study derives from the observation that a correlation exists between failed first attempts (FFA) at embryo transfer caused by one or more embryos remaining in the catheter and reduced pregnancy rates (20.3 vs 3.0%). The aim of this study was to examine the relationship between failed first attempts at transfer and contamination of the transfer set; the related aspects of cervix dilatation and late embryo transfer were also investigated.Results The following observations were made. Retention of embryos in the transfer sets significantly reduced the pregnancy rate (P =0.015); catheters contaminated with blood and cervical mucus indirectly contributed to this effect by increasing the incidence of failed first transfer attempts. Even though cervical dilatations, if indicated by uterus sounding, were done 2 days before embryo transfer, no pregnancies were effected in these 18 cases (P =0.0001). Late transfers of embryos, due to delayed fertilization or slow cleavage rates, yielded a pregnancy rate of 10.5%. Conclusion The approach of immediately retransferring retained embryos does not solve the problem of reduced pregnancy rates in FFA cases. It is suggested that ET should be repeated 1 day later in FFA cases in an attempt to improve pregnancy rates.     

冻融胚胎移植中辅助孵化对妊娠结局及安全性的影响

目的探讨在玻璃化冻融胚胎移植(FET)中,激光辅助孵化(AH)操作后对妊娠结局及母儿安全性的影响。方法回顾性分析2014年1月—2015年10月接受体外受精-胚胎移植(IVF-ET)失败后行FET患者的临床资料,根据患者年龄进行分组后比较AH操作后妊娠结局及母儿并发症的发生情况。结果在正常年龄组(38岁)的患者中,未行AH操作的对照组中胚胎种植率、临床妊娠率、活产率、多胎率均高于AH组,流产率低于AH组,并且差异有统计学意义(P0.05);在高龄(≥38岁)患者中,AH组的胚胎种植率、临床妊娠率较对照组有增高的趋势(P0.05);分娩周期中,AH组与对照组早产率、死胎率、母体并发症、新生儿男女比例、胎龄、出生体质量、新生儿缺陷率等均无统计学差异(P0.05)。结论对于正常年龄患者,卵裂期FET时不建议行AH操作;对于高龄患者,AH操作可提高胚胎种植率及临床妊娠率,但不能明显改善其妊娠结局;AH对母儿安全暂无不良影响。     

Serum progesterone concentrations on the day after human chorionic gonadotropin administration and progesterone/oocyte ratios predict in vitro fertilization/embryo transfer outcome

Purpose In gonadotropin-releasing hormone analogue-pretreated in vitro fertilization-embryo transfer cycles, pregnancy rates are inversely related to serum progesterone levels on the day of administration of human chorionic gonadotropin. The relationship of the progesterone concentration on other days in the periovulatory period to pregnancy rates in such cycles is little studied. We therefore retrospectively analyzed the relationship between progesterone concentrations on the day after human chorionic gonadotropin and pregnancy in 114 cycles, 28 and 23 of which produced clinical and ongoing/delivered pregnancies, respectively. To assess the effect of the extent of follicular luteinization on success, we also studied the relationship between the progesterone concentration per oocyte retrieved and pregnancy for the day of and day after human chorionic gonadotropin.Results Progesterone concentrations on the day after human chorionic gonadotropin were inversely associated with clinical pregnancy by multiple logistic regression analysis (P<0.05). Progesterone/oocyte ratios were inversely associated with clinical pregnancy (P<0.05) and ongoing/delivered pregnancy (P<0.02) for both the day of and the day after human chorionic gonadotropin.Conclusion The study results extend the window of time during which elevated progesterone concentration is associated with poor outcome to at least 2 days. This finding is consistent with hypothetical mechanisms attributing the link between progesterone concentration and outcome to either endometrial or follicle/oocyte events. The association of lack of follicular luteinization (low progesterone per oocyte ratios) and favorable outcome suggests a predominant effect of progesterone on follicle/oocyte quality. Further studies are needed to clarify the mechanisms underlying the association between progesterone and in vitro fertilization-embryo transfer outcome.     

体外受精—胚胎移植后发生宫内外同时妊娠6例临床分析

目的 探讨体外受精-胚胎移植（IVF-ET）后宫内外同时妊娠（HP）的发生率、危险因素、诊断及防治方法。方法 对IVF-ET后发生宫内外同时妊娠6例病例进行回顾性分析。结果 宫内外同时妊娠的发生率为0.95%。6例病人均移植3个以上胚胎,4例有盆腔或输卵管疾病史;宫内外同时妊娠症状以腹痛为主。2例伴腹肌紧张及低血容量休克。3例有阴道流血,6例病人中2例经B超确诊,3例经手术确诊。1例误诊为阑尾炎。1例行输卵管修补术,余行输卵管切除术治疗,其中2例自然分娩活婴。结论 IVF-ET后HP发生率明显增加,特别是有盆腔、输卵管疾病史或移植多个胚胎者。加强B超监测。有助于在妊娠部位破裂前发现、诊断及治疗HP,防止不良后果发生。     

体外受精-胚胎移植中暂时性高催乳素血症对妊娠的影响

目的探讨在体外受精与胚胎移植(IVF-ET)中,注射人绒毛膜促性腺激素(HCG)日血清催乳素(PRL)浓度对妊娠的影响。方法回顾性分析2005年10月至2008年3月期间127个体外受精与胚胎移植周期的资料。结果在控制性卵巢刺激(COS)中,按注射HCG日血清催乳素浓度不同分4组,依次为<30ng/mL(A组),≥30～<60ng/mL(B组),≥60～<90ng/mL(C组),≥90ng/mL(D组)。体外受精与胚胎移植的种植率分别为13.68%、24.16%、15.90%、2.86%;临床妊娠率分别为25.00%、47.17%、29.41%、7.69%。各组的种植率及临床妊娠率差异有统计学意义(χ2检验,P值分别为0.018和0.019)。进一步进行两两比较,HCG日PRL≥90ng/mL(D组)的种植率及妊娠率明显较PRL水平≥30～<60ng/mL(B组)低,差异有统计学意义(P值分别为0.005和0.009)。结论控制性卵巢刺激后血清催乳素浓度较基础水平明显升高,导致暂时性高催乳素血症。当HCG注射日血清催乳素明显升高(≥90ng/mL)时,体外受精与胚胎移植的种植率及临床妊娠率明显下降。对控制性卵...     

高催乳素血症患者体外受精-胚胎移植妊娠结局的临床分析

目的分析无症状的高催乳素血症（hyperprolactinemia,HPRL）患者接受体外受精-胚胎移植（IVF-ET）助孕治疗时的妊娠结局。方法回顾性分析217例确诊高催乳素血症患者接受IVF-ET助孕治疗的临床资料,同期121例输卵管因素行IVF而血清催乳素水平正常的患者为对照组,比较分析卵泡数、获卵数、受精率、临床妊娠率、胚胎着床率及妊娠结局等。结果两组间促性腺激素使用刺激时间、促性腺激素用量、获卵数、HCG日内膜厚度、受精率差异无统计学意义（P〉0.05）。高催乳素血症患者的临床妊娠率及着床率显著低于对照组（P〈0.05）。血清催乳素水平低于50 ng/ml的患者,经多巴胺受体激动剂治疗进入IVF周期前血清泌乳素水平高于25 ng/ml组,与血清催乳素水平正常组比较,获卵数、受精率、临床妊娠率、着床率和妊娠结局差异无统计学意义（P〉0.05）。结论高催乳素血症会对IVF结局产生不利影响。血清催乳素水平低于50 ng/ml可以进入IVF周期,不影响促排卵和妊娠结局。     

Ectopic pregnancies after in vitro fertilization and embryo transfer

Objective Our objective was to analyze the risk factors, stimulation characteristics, and future fecundity of patients with ectopic pregnancies after in vitro fertilization (IVF).Methods We retrospectively evaluated all cases of ectopic pregnancy occurring between January 1989 and March 1993 (Cornell series 1 to 17). A case-control group of intrauterine pregnancies was used for comparison of the stimulation and transfer characteristics.Results Twenty-seven of 1123 pregnancies (2.4%) were ectopic, following 2812 fresh IVF embryo transfers, while 8 of 105 pregnancies (7.6%) were ectopic, following 405 frozen-thawed embryo transfers. Tubal factor was the cause of infertility in the majority (85.7%) of ectopic pregnancies. No difference was found between the ectopics and the matched controls in stimulation and transfer characteristics. Thirty ectopic pregnancies were ampullary, two were interstitial, two were cervical, and one was heterotopic. Twenty of the patients subsequently underwent 29 IVF attempts, with a pregnancy rate of 41.4% per transfer.Conclusions Ectopic pregnancy after IVF appears to be related to preexisting tubal pathology; embryo transfer of cryopreserved thawed embryos in a natural cycle may result in a higher ectopic rate in these patients; in subsequent IVF cycles the intrauterine pregnancy rate of these patients is not decreased.