The usefulness of ultrasound guidance in frozen-thawed embryo transfer: a prospective randomized clinical trial

BACKGROUND: Recent randomized controlled trials have shown that implantation and pregnancy rates were improved with ultrasound-guided embryo transfer compared with clinical touch in fresh IVF cycles associated with supraphysiological ovarian steroid levels. However, the usefulness of ultrasound guidance in frozen-thawed embryo transfer where potential hormonal influences are lacking has not been appropriately investigated. METHODS: A total of 184 consecutive patients undergoing thawed embryo transfer cycles with hormone replacement under pituitary suppression were randomized by computer-generated randomization table to two study groups: 93 had ultrasound-guided (group 1) and 91 had clinical touch (group 2) embryo transfer. RESULTS: There was equal distribution between the two study groups with respect to the main demographic and baseline characteristics of the patients as well as the characteristics of both prior IVF cycles from which embryos were generated and cryopreserved-thawed embryo transfer cycles. However, both pregnancy and implantation rates in group 1 (34.4 and 19.8% respectively) were significantly higher than the corresponding values (19.7 and 11.9%) in group 2. CONCLUSIONS: Ultrasound guidance in frozen-thawed embryo transfer significantly increases pregnancy and implantation rates.     

卵裂期胚胎提前解冻培养过夜对冻融移植周期临床结局的影响

目的探讨玻璃化冻融周期中卵裂期胚胎当天解冻移植和提前1天解冻过夜培养后移植对妊娠结局的影响。方法选择武汉大学中南医院生殖医学中心2015年1月-2018年6月的414个冻融卵裂期胚胎移植周期进行回顾性分析。根据胚胎解冻和培养的时间点,分为当日解冻组(A组,207个周期)和提前解冻组(B组,207个周期);根据患者的年龄,A组B组又分别分成3个亚组,即年龄<30岁(A1,B1);年龄31~35岁(A2,B2)和年龄>35岁(A3,B3),比较各组间的种植率、临床妊娠率、活产率及流产率等的差异。结果A1组与B1组的临床妊娠率、种植率、活产率及流产率分别为47%vs 65.3%,30.3%vs 45.4%,36.4%vs 52.3%,15%vs 13.9%;A2组与B2组的临床妊娠率、种植率、活产率及流产率分别为54.8%vs 71.8%,38.2%vs 51.5%,46.6%vs 60.7%,21.9%vs17.6%;A3组与B3组的临床妊娠率、种植率、活产率及流产率分别为38.2%vs 52.9%,24.8%vs 37.3%,25%vs 36.8%,35.5%vs 29.2%;提前解冻在不同年龄组均可显著改善妊娠结局,差异均有统计学意义(P<0.05)。此外,无论是否提前解冻,年龄>35岁组的活产率均显著低于≤30岁组和31岁~35岁组(P<0.05),而妊娠率和种植率较其他两组亦呈现降低趋势,但差异无显著性。结论冻融卵裂期胚胎提前解冻培养后再进行移植能改善妊娠结局,并且随着女性年龄的增高,活产率均会随之下降。     

A prospective randomized study to assess the benefit of partial zona pellucida digestion before frozen-thawed embryo transfers

BACKGROUND: Assisted hatching (AH) in fresh embryo transfer (ET) could be associated with increased implantation rates. However, very few prospective randomized studies have specifically addressed the issue of AH during frozen-thawed embryo transfers (FET) cycles, those that have reported controversial results. The aim of this study was to evaluate the benefit of an enzymatic zona pellucida treatment of frozen-thawed embryos before transfer. METHODS: This was a prospective study including 125 non-donor FET cycles from 125 infertile couples. FETs were randomly allocated into AH group (n = 61, embryos pretreated with pronase 5 IU/ml for 1 min at 37 degrees C) or control group (n = 64, untreated embryos). Zona pellucida thickness was measured for each transferred embryo. The main outcome parameters were clinical pregnancy and implantation rates. RESULTS: The two groups were comparable regarding mean women's age, duration and indications of infertility, IVF outcome after fresh ETs, numbers and quality of fresh and frozen embryos, frozen-thawed embryo survival rates and blastomeres survival indexes. Despite a statistically significant decrease of zona pellucida thickness after pronase treatment [(mean +/- SD) 18.5 +/- 2.25 versus 14.5 +/- 2.75 microm; P < 0.0001], implantation (9.6 versus 9.2%) and clinical pregnancy rates (18.0 versus 17.2%) were not statistically different after FETs, with a similar mean number of embryos transferred between AH and control groups, respectively. CONCLUSION: Within the constraints of our protocol, partial enzymatic digestion of zona pellucida by pronase was not related with any benefit of the FET outcome especially concerning the implantation ability of frozen-thawed embryos.     

Cryo-thawed embryos obtained from conception cycles have double the implantation and pregnancy potential of those from unsuccessful cycles

BACKGROUND: The purpose of this study was to evaluate the influence of fresh IVF/ICSI cycle outcome on the prognosis of the related frozen embryo replacement (FER) cycle. METHODS: 459 FER cycles, involving 2049 cleavage stage embryos with no or up to 10% fragmentation, were performed for which the outcome of the fresh cycle was recorded. The cycles were divided into two groups; group A included cycles in which cryopreserved embryos were obtained from fresh cycles in which conception occurred. Group B were cycles in which cryopreserved embryos originated from unsuccessful fresh cycles. RESULTS: Groups A and B were comparable with respect to mean (+/- SD) age at cryopreservation (33 +/- 3.9 versus 33.2 +/- 4 years, P = not significant), mean number of oocytes retrieved and fertilized normally in the fresh cycle (11 +/- 5.2 versus 11.2 +/- 4.8, P = not significant) and mean age at the cryo-thawed transfer (34.5 +/- 4.2 versus 33.9 +/- 4 years, P = not significant). No significant difference was found between the two groups with regard to mean number of embryos cryopreserved (6.5 +/- 3.9 versus 6.2 +/- 3.6) and subsequently thawed (4.5 +/- 2.5 versus 4.5 +/- 1.8) per cycle and number of cryo-thawed embryos transferred per cycle (2.0 +/- 0.7 versus 2.1 +/- 0.8). However, the implantation rate per transferred embryo in group A was double that in group B (23 versus 11.2%, P < 0.0001). Moreover, the clinical pregnancy and ongoing pregnancy rates per cycle were significantly higher in group A compared with group B (34.8 and 27.3% versus 15.6 and 13.1%, P < 0.0001 and P = 0.0003 respectively). The difference in FER cycle outcome could not be explained by confounding variables. CONCLUSIONS: After thawing, cryopreserved embryos originating from conception IVF/ICSI cycles achieve double the implantation and pregnancy rates of those obtained from unsuccessful cycles.     

A randomized study comparing IVF in the unstimulated cycle with IVF following clomiphene citrate

The efficiency of IVF in unstimulated cycles was compared with that following ovarian stimulation with clomiphene citrate in a simple protocol with ultrasound monitoring only. A total of 132 couples with no previous IVF attempts, selected by female age <35 years, indication for intracytoplasmic sperm injection or infertility caused by tubal factor or unexplained infertility were randomized to the two protocols. Randomization yielded two comparable groups. The clomiphene group (68 couples) performed significantly better than the unstimulated group (64 couples) in terms of number of cycles with oocyte harvest (90/111 or 81% versus 65/114 or 57%; chi(2) = 9.21, P < 0.002), embryo transfers per started cycle (59/111 or 53% versus 29/114 or 25%; chi(2) = 18.14, P < 0.0001), live intrauterine pregnancy rate per started cycle (20/111 or 18% versus 4/114 or 4%; chi(2) = 12.42, P < 0.0001), live intrauterine pregnancy rate per embryo transfer (20/59 or 34% versus 4/29 or 14%; chi(2) = 3.96, P = 0.047), but not in terms of implantation rate (22/85 or 26% versus 4/29 or 14%; chi(2) = 1.65). Only two twin pregnancies occurred. Modest side-effects were recorded following clomiphene. Accordingly, a simple clomiphene citrate protocol, but not IVF in unstimulated cycles, seems compatible with the concept of 'friendly IVF', yielding a fair pregnancy rate both per cycle started and per embryo transfer in selected patients. The results do not substantiate any important negative anti-oestrogenic effects of clomiphene.     

Implantation and pregnancy rates in relation to oestradiol and progesterone profiles in cycles with and without the use of gonadotrophin-releasing hormone agonist suppression

The oestradiol (E2), progesterone (P4) levels, the corresponding E2/P4 ratios and pregnancy and implantation rates were studied in 565 in-vitro fertilization (IVF) cycles stimulated with gonadotrophins alone and in 320 cycles stimulated with adjunctive treatment of a gonadortrophin-releasing hormone agonist (GnRHa, leuprolide). The overall pattern of serum E2 and P4 levels and the E2/P4 ratios were similar in both groups, though significantly higher absolute levels were demonstrated in leuprolide cycles. Similar profiles were observed in conception and nonconception cycles within each group; significantly higher levels were noted in conception cycles starting nine days after embryo transfer. Though the overall pregnancy rate per fresh transfer in leuprolide cycles was significantly higher than in non-leuprolide cycles (32 versus 22%, P less than 0.001), this was largely due to the transfer of more embryos; the implantation rate per embryo transferred did not differ significantly between groups (11.8 versus 10.5%). We conclude that the use of GnRHa in IVF cycles increases the pregnancy rate as a consequence of more embryos being transferred, since implantation rate was unaltered by GnRHa. Further, GnRHa does not alter the basic E2 and P4 progesterone pattern observed in gonadotrophin-stimulated cycles (though the absolute levels are higher); moreover, these patterns could not be used to predict pregnancy outcome.     

Shortened exposure of oocytes to spermatozoa improves in-vitro fertilization outcome: a prospective, randomized, controlled study.

A prospective, randomized study of 158 patients undergoing in-vitro fertilization (IVF) and embryo transfer was conducted to evaluate whether a shortened exposure of oocytes to spermatozoa enhances oocyte development, and subsequently influences the IVF outcome. A comparison was made between conventional treatment time and shorter exposure of retrieved oocytes to spermatozoa. Fertilization and cleavage rates, embryo quality, implantation and pregnancy rates in the study group (short exposure) versus controls (standard IVF procedure) were evaluated. Fertilization (56 versus 61%) and cleavage rates (96 versus 92%) were similar in the two groups respectively. However, embryo quality was significantly higher in the study group (P < 0.05). Moreover, the pregnancy and implantation rates were significantly increased (42.4 versus 26% per embryo transfer, and 16 versus 10% respectively; P < 0.05). Our results demonstrated that shorter exposure of oocytes to spermatozoa is superior to the standard time in IVF and may have a favourable effect on implantation rates by improving embryo quality.     

Low dose prednisolone administration in routine ICSI patients does not improve pregnancy and implantation rates

BACKGROUND: Glucocorticoids have been used in conjunction with zona dissection to improve pregnancy and implantation rates in IVF patients. The aim of this prospective randomized study was to evaluate the effect of low-dose prednisolone in addition to the standard protocol, on pregnancy and implantation rates in routine ICSI patients before and after embryo replacement. METHODS: A total of 313 patients in 360 consecutive cycles (patients <39 years old and with three or less than three ICSI attempts) performed at our centre were randomly assigned by computer-generated list to receive either prednisolone (10 mg/day in two divided doses), starting on the first day of ovarian stimulation and continuing for 4 weeks (group A), or no treatment (group B). RESULTS: The mean age, number of previously failed IVF attempts, basal FSH levels and the mean rank of trials were comparable between groups A and B. The mean (+/- SD) number of metaphase II oocytes retrieved (11.9 +/- 5.5 versus 12.0 +/- 5.1), 2-pronuclei fertilization rate (67.2 versus 65.8%), the pregnancy and the implantation rates were not different between the study and control groups (49.0 and 23.6% versus 50.0 and 23.3% respectively). CONCLUSION: Low-dose prednisolone treatment in addition to the standard protocol before and after embryo replacement does not appear to have a significant effect on pregnancy or implantation rates.     

Progesterone supplementation increases luteal phase endometrial thickness and oestradiol levels in in-vitro fertilization.

Luteal phase supplementation with natural progesterone appears to increase the pregnancy rate in in-vitro fertilization (IVF). The objective of this investigation was to examine the effect of intravaginal progesterone on endometrial thickness and hormonal parameters 7-9 days after embryo transfer. IVF patients receiving progesterone supplementation (Prog +, n = 64), who did not conceive, were compared to patients not receiving progesterone (Prog -, n = 23) because of failed fertilization. These two groups were also compared to 20 women (Preg) who conceived and to 16 women (control) in the mid-luteal phase of natural cycles. Endometrial thickness was greater (P < 0.01) in the Prog + (0.88 +/- 0.04 cm) and Preg (0.92 +/- 0.02 cm) groups compared to the Prog - (0.71 +/- 0.05 cm) and control (0.65 +/- 0.05 cm) groups. Mean luteal phase serum oestradiol levels were also higher (P < 0.05) in the Prog + (1118 +/- 112 pmol/l) and Preg (2267 +/- 757 pmol/l) groups than in the Prog - (574 +/- 70 pmol/l) and control (468 +/- 38 pmol/l) groups. These findings suggest that progesterone supplementation may affect pregnancy rates in IVF by increasing endometrial thickness, thereby enhancing receptivity for implantation. The mechanism through which this effect occurs is unclear but may involve serum oestradiol elevation.     

A rapid decline in serum oestradiol concentrations around the mid-luteal phase had no adverse effect on outcome in 763 assisted reproduction cycles

Progesterone is essential in the luteal phase whereas luteal oestradiol may play only a permissive role on the endometrium. However, a rapid decline in oestradiol concentrations around the mid-luteal period may compromise the endometrial integrity leading to poor IVF outcomes. A retrospective analysis of 763 women aged <40 years undergoing their first IVF cycle and having < or =3 embryos replaced was undertaken. In cycles receiving human chorionic gonadotrophin (HCG) for luteal support, 25th, 50th and 75th centiles of the ratio of day-of-HCG oestradiol to mid-luteal oestradiol (oestradiol ratio) were 1.8, 2.8 and 5.0 respectively. Hormonal parameters were not different between pregnant and non-pregnant cycles. The outcomes were similar irrespective of the oestradiol ratio. Progesterone supplementation was used instead when the HCG oestradiol was >18 000 pmol/l or there were features of ovarian hyperstimulation syndrome. Pregnancy rates of these hyperstimulated cycles were 16.7 and 11.4% per cycle respectively when oestradiol ratio was < or =5.0 and >5.0. This difference did not reach statistical significance. Our results could not find an adverse outcome in cycles showing a rapid decline in oestradiol during the mid-luteal phase.     

人工周期方案下冻融胚胎移植的安全性评价

目的 评价人工周期方案下行冻融胚胎移植(FET)的安全性.方法 2004年1月至2008年6月本院进行的1397个FET周期分2组:即人工周期组[人工周期方案(戊酸雌二醇片+黄体酮针),420个周期]和自然周期组(对照组,自然周期方案,977周期).比较两组间临床妊娠率、种植率、分娩率、流产率、异位妊娠率、多胎妊娠率、单胎低出生体质量率、单胎早产率及出生缺陷率等指标,评价人工周期方案下FET的安全性.结果 人工周期组和自然周期组的临床妊娠率[26.2%(110/420)和23.9%(233/977)]、种植率[13.7%(142/1034)和12.6%(299/2369)]、分娩率[69.1%(76/110)和76.0%(177/233)]、流产率[22.7%(25/1 10)和18.0%(42/233)]、异位妊娠率[2.7%(3/110)和3.0%(7/233)]、多胎妊娠率[26.4%(29/110)和24.9%(58/233)]、单胎低出生体质量率[1.6%(1/63)和4.4%(6/138)]、单胎早产率[9.5%(6/63)和7.3%(10/138)]、出生缺陷率[0%(0/420)和0%(0/977)]、男胎分娩率[53.8%(43/80)和54.2%(96/177)]及女胎分娩率[46.2%(37/80)和45.8%(81/177)]差异均无统计学意义(P>0.05).结论 近期评价人工周期方案下行FET是安全的.     

eSET irrespective of the availability of a good-quality embryo in the first cycle only is not effective in reducing overall twin pregnancy rates

INTRODUCTION: In several clinics, elective single-embryo transfer (eSET) is applied in a selected group of patients based on age and the availability of a good-quality embryo. Whether or not eSET can be applied irrespective of the presence of a good-quality embryo in the first cycle, to further reduce the twin pregnancy rate, remains to be elucidated. METHODS: In patients <38 years two transfer strategies were compared, which differed in the first cycle only: group A (n = 141) received eSET irrespective of the availability of a good-quality embryo, and group B (n = 174) received eSET when a good-quality embryo was available while otherwise they received double embryo transfer (DET; referred to as eSET/DET transfer policy). In any subsequent cycle, in both groups the eSET/DET transfer policy was applied. RESULTS: After completion of their IVF treatment (including a maximum of three fresh cycles and the transfer of frozen-thawed embryos), comparable cumulative live birth rates (62.4% in group A and 62.6% in group B) and twin pregnancy rates (10.1 versus 13.4%) were found. However, patients in group A required significantly more fresh (2.0 versus 1.8) and frozen (0.8 versus 0.5) cycles. CONCLUSIONS: The transfer of one embryo in the first cycle, irrespective of the availability of a good-quality embryo, in all patients <38 years, is not an effective transfer policy for reducing the overall twin pregnancy rate.     

Prevention of severe ovarian hyperstimulation syndrome in IVF with or without ICSI and embryo transfer: a modified 'coasting' strategy based on ultrasound for identification of high-risk patients

Ovarian hyperstimulation syndrome (OHSS) can be a severe and potentially life-threatening complication of ovarian stimulation for IVF. Coasting or withholding gonadotrophin stimulation relies on frequent estimation of serum oestradiol to identify patients at risk. A modified coasting protocol was developed in which identification of patients at risk of severe OHSS was based on ultrasound monitoring. Serum oestradiol concentrations were measured only in patients with >20 follicles on ultrasound (high risk). If serum oestradiol concentrations were <3000 pmol/l, the gonadotrophin dose was maintained; if concentrations were >/=3000 pmol/l but <13200 pmol/l and >/=25% of the follicles had a diameter of >/=13 mm, the gonadotrophin dose was halved; and if serum oestradiol concentrations were >/=13 200 pmol/l and >/=25% of the follicles had a diameter of >/=15 mm, patients were coasted. In the latter group, human chorionic gonadotrophin (HCG) 10000 IU was administered when at least three follicles had a diameter of >/=18 mm and serum oestradiol concentrations were <10000 pmol/l. Over a 10 month period, serum oestradiol concentrations were measured in 123 out of 580 cycles (24%) and in 50 cycles, gonadotrophins were withheld. Overall, moderate OHSS occurred in three patients (0.7%) and severe OHSS in one patient (0.2%). The pregnancy rates in the cycles where the gonadotrophin dose was reduced or withheld were 39.6 and 40% per cycle respectively; corresponding implantation rates were 30.7 and 25.6%. It is concluded that the modified coasting strategy is associated with a low risk of moderate and severe OHSS to a minimum without compromising pregnancy rates. Identification of patients at risk by ultrasound reduces the number of serum oestradiol measurements and thus inconvenience to patients as well as costs and workload.     

High pregnancy rates and successful prevention of severe ovarian hyperstimulation syndrome by 'prolonged coasting' of very hyperstimulated patients: a multicentre study

In a multicentre trial, 65 in-vitro fertilization (IVF)-embryo transfer cycles were severely hyperstimulated. Instead of cancelling the cycle, gonadotrophins were withheld for a 'coasting period' until serum oestradiol concentrations had dropped below 10,000 pmol/l (mean 4.3 days), and then human chorionic gonadotrophin was administered. Four cycles were cancelled and there were 61 oocyte aspirations. A total of 103 fresh embryos was transferred to 53 patients, resulting in a pregnancy rate of 42% per started cycle (51% per embryo transfer), with an implantation rate of 31%. Only one patient developed severe ovarian hyperstimulation syndrome (OHSS). Four patients developed moderate OHSS. In all, two patients were hospitalized for OHSS. In order to optimize the coasting procedure, it seems important that each IVF centre identifies its appropriate cut-off limits for serum oestradiol concentrations and follicle size for initiating and ending of the coasting period. Correctly handled, it seems to be a major advance in the search for improved stimulation policies for high-responders.     

Morphometric analysis of peri-implantation endometrium in patients having excessively high oestradiol concentrations after ovarian stimulation

The present study investigated whether high oestradiol concentrations after ovarian stimulation in infertile women affect endometrial development around the time of implantation. The glandular and stromal components of the endometrium were assessed by morphometric criteria. Endometrial biopsies were taken on day 7 (+/-1) after the ovulating dose of human chorionic gonadotrophin in stimulation cycles and on day 7 after the LH surge in natural cycles. Women (n = 38) undergoing assisted reproduction treatment were evaluated: 12 women in natural cycles, 11 women in stimulation cycles with oestradiol <20,000 pmol/l and failed fertilization after oocyte collection (moderate responders) and 15 women with an oestradiol concentration of > or =20,000 pmol/l in stimulation cycles (high responders). High responders showed delayed glandular maturation and advanced stromal morphology, whereas moderate responders demonstrated synchronous development of glandular and stromal features. In natural cycles, the glands were in phase. The effect of excessively high oestradiol concentrations could be explained by quantitative evaluation of the endometrial biopsies as gland--stromal dyssynchrony, which indicates a deficient secretory transformation of the endometrium that represents a suboptimal endometrial environment for implantation. This substantiates our previous clinical observation of significantly lower pregnancy rates in IVF cycles of women with high oestradiol concentrations (> or =20,000 pmol/l).     

Embryo transfer under ultrasound guidance improves pregnancy rates after in-vitro fertilization

Between October 1998 and January 1999, we examined the influence of ultrasound guidance in embryo transfer on pregnancy rate in 362 patients from our in-vitro fertilization (IVF)-embryo transfer programme. These patients were prospectively randomized into two groups: 182 had ultrasound-guided embryo replacement, and 180 had clinical touch embryo transfer. There were no statistically significant differences between the two groups with respect to age, cause of infertility and in the characteristics of the IVF cycle. The pregnancy rate was significantly higher among the ultrasound-guided embryo transfer group (50%) compared with the clinical touch group (33.7%) (P < 0.002). Furthermore, there was also a significant increase in the implantation rate: 25.3% in the ultrasound group compared with 18.1% in the clinical touch group (P < 0.05). In conclusion, ultrasound assistance in embryo transfer significantly improved pregnancy and implantation rates in IVF.     

Relationship between the threshold of ovarian sensitivity to human menopausal gonadotrophin stimulation and in-vitro fertilization treatment outcome

In a retrospective study of 813 oocyte retrieval–embryotransfer cycles in women with normal follicle stimulating hormoneand luteinizing hormone concentrations, we sought to investigatethe relationship between the amount of human menopausal gonadotrophin(HMG) used for ovarian stimulation and treatment outcome. Patientswere divided into three groups: group A patients (495 cycles)required <40 ampoules of HMG and had a predicted probabilityfor pregnancy of 25% per embryo transfer; group B patients (165cycles) required 41–77 ampoules per cycle, with a predictedprobability rate for pregnancy of 5–25% per embryo transfer;and group C patients (153 cycles) required >77 ampoules ofHMG and the predicted probability for pregnancy was <5% perembryo transfer. Groups C and A differed significantly (P <0.005). The mean oestradiol concentration on the day of HCGadministration in group C was 6412 pmol/l, and the mean numberof eggs retrieved was seven. The highest success rates werefound when up to 2.5 ampoules of HMG were required for eachegg or 4.4 ampoules for each embryo. The lowest rates were obtainedwhen >4.8 ampoules of HMG were necessary for each oocyteor >9.6 ampoules for each embryo (P < 0.005). We identifieda group of infertile patients who required excessive amountsof HMG to achieve a fair degree of steroidogenesis, number ofeggs and number of embryos but who had very low pregnancy rates.Although all other relevant parameters were normal, this mayhighlight the beginning of ovarian–gamete insufficiencybefore the basic hormonal status is affected. In cases of repeatedfailure, oocyte donation should be considered.     

GnRH agonist versus GnRH antagonist in oocyte donation cycles: a prospective randomized study

BACKGROUND: The specific role of LH in folliculogenesis and oocyte maturation is unclear. GnRH antagonists, when administered in the late follicular phase, induce a sharp decrease in serum LH which may be detrimental for IVF outcome. This study was performed to evaluate whether the replacement of GnRH agonist (triptorelin) by a GnRH antagonist (ganirelix; NV Organon) in oocyte donation cycles has any impact on pregnancy and implantation rates. METHODS: A total of 148 donor IVF cycles was randomly assigned to use either a GnRH antagonist daily administered from the 8th day of stimulation (group I) or a GnRH agonist long protocol (group II) for the ovarian stimulation of their donors. The primary endpoints were the pregnancy and the implantation rates. RESULTS: The clinical pregnancy rate per transfer (39.72%, 29/73 versus 41.33%, 31/75) based on transvaginal scan findings at 7 weeks of gestation, the implantation rate (23.9 versus 25.4%) and the first trimester abortion rate (10.34 versus 12.90%) were similar in the two groups. CONCLUSION: In oocyte donation cycles the replacement of GnRH agonist by a GnRH antagonist appears to have no impact on the pregnancy and implantation rates when its administration starts on day 8 of stimulation.     

Towards defining parameters for a successful single embryo transfer in frozen cycles

BACKGROUND: Twin pregnancies in IVF should be avoided by transferring embryos one at a time, even for frozen cycles. In this study, we investigated the effect of blastomere lysis and cleavage in singleton frozen embryo transfer (sFET) cycles. Outcomes were compared with the transfer of two embryos in frozen transfer cycles (dFET). METHODS: A retrospective analysis was performed on 891 FET cycles, involving 404 sFET and 487 dFET cycles. RESULTS: Overall, in sFET cycles, the pregnancy and implantation rates were 8.9 and 8.7%. When blastomere lysis was more than 25% but no greater than 50%, the pregnancy and implantation rates were 3.2%. If blastomere lysis was greater than 50% there were no pregnancies. If blastomere lysis was less than 25%, but with no cleavage, the pregnancy and implantation rates were 4.1%. The results significantly improved (P = 0.007) in the group with less than 25% lysis, when cleavage occurred. The pregnancy and implantation rates for this group were 17.3 and 16.6%. This was not significantly different from unselected two embryo transfers (22 and 12.7%,P = 0.2 and 0.19, respectively). There were 21 twins with dFET (19.6% of pregnancies) and none in sFET. CONCLUSION: Both blastomere lysis and cleavage affect the outcome in sFET. To avoid the risk of twins, sFET should be considered when the embryo shows less than 25% blastomere lysis and at least one blastomere cleaves.     

An aggressive philosophy in controlled ovarian stimulation cycles increases pregnancy rates

To assess the effect of timing of human chorionic gonadotrophin(HCG) administration in ovarian stimulation cycles, the serumoestradiol concentration and follicle profile were comparedwith the clinical pregnancy rate in 582 ovarian stimulation— intra-uterine insemination (OS—IUI) cycles and3917 in-vitro fertilization—embryo transfer (IVF—ET)cycles. The pregnancy rates increased exponentially with increasingoestradiol in both OS—IUI and IVF—ET cycles (R²= 0.720, P < 0.001) but then decreased in OS-IUI cycles whenthe oestradiol concentration exceeded 5000 pmol/l (R² = 0.936,P < 0.004) at HCG administration. In OS—IUI cyclesthe percentage of cycles with three or more mature follicles( 18 mm diameter) increased up to an oestradiol concentrationof 5000 pmol/l then declined, mirroring the pregnancy rate (R²= 0.900, P = 0.01). The exponential increase in pregnancy ratewith increasing oestradiol concentration in IVF—ET cyclessuggests that high oestradiol concentration does not have adeleterious effect on endometrial receptivity. The decreasein pregnancy rate in OS-IUI cycles when oestradiol concentrationexceeded 5000 pmol/l reflected fewer mature follicles, resultingfrom premature administration of HCG to avoid severe ovarianhyperstimulation syndrome (OHSS). We recommend that HCG administrationbe delayed until multiple follicles have reached maturity, andreducing the risk of severe OHSS by converting high risk OS—IUIcycles to IVF—ET, or if funds or facilities are unavailable,transvaginally draining all but four or five mature follicles.