Biochemical monitoring during hormone replacement therapy cycles for transfer of cryopreserved embryos in patients with functional ovaries.

Biochemical monitoring was undertaken in 22 treatment cycles for women with normal ovarian function who underwent pituitary suppression with buserelin and administration of exogenous oestradiol (E2) and progesterone (P) for cryopreserved embryo transfer (ET). Eighteen transfers of 1-4 thawed embryos, on the third day of exposure to progesterone, resulted in five clinical pregnancies (27.8%) and one biochemical pregnancy. There was no difference between pregnant and non-pregnant patients in the number and quality of embryos transferred, age, weight or infertility diagnosis. Serum E2 level from days 10-17 (the late proliferative phase) of the therapy cycle were significantly higher in the pregnant group compared with the non-pregnant group (P less than 0.05--P less than 0.005). There were no significant differences in P levels between the two groups from the onset of progesterone administration to the end of the cycle. However, as might be expected, the mean E2/P molar ratio in the pregnant group was significantly higher at the time of ET (P less than 0.02). It is concluded that biochemical monitoring during the embryo replacement cycle is necessary to tailor drug dosages for individual requirements to achieve adequate E2 levels before ET. Alternative routes of oestradiol administration need to be considered in patients with poor E2 profiles.     

A flexible protocol for the induction of recipient endometrial cycles in an oocyte donation programme

Synchronization of the availability of good quality oocytesfrom donors and adequate endometrial maturation of recipientsare very important for the success of an oocyte donation programme.A flexible protocol for the endometrial preparation of recipientsis important in timing embryo transfer between days 17 and 19of the cycle (‘window of receptivity’). The purposeof this study was to evaluate the effect of the length of oestradioladministration to recipients on pregnancy outcome. Oestrogenadministration was 8 mg/day, but its length varied prospectivelyfrom 6 to 27 days, followed by the addition of progesterone(100 mg daily Lm.) for 2–4 days according to the availabilityof good quality oocytes. Pregnancy outcome was evaluated regardlessof age, indication for oocyte donation or number of embryostransferred per patient The pregnancy rate per cycle was comparablewhen oestradiol was administered from 6 to 11 days before progesteroneaddition, while it dropped significantly thereafter. The variationin progesterone administration did not affect pregnancy outcome.These findings provide us with a greater flexibility by allowingus to vary oestradiol administration to recipients from 6 to11 days prior to progesterone, reducing considerably, therefore,the need to cancel embryo transfer because of oocyte unavailability.Thus we can arrange to transfer embryos between days 17 and19 of the recipient's cycle so as to obtain the best possibleclinical outcome.     

Ultrasound-guided embryo transfer maximizes the IVF results on day 3 and day 4 embryo transfer but has no impact on day 5

BACKGROUND: The use of ultrasound-guided embryo transfer has been reported to affect success rates in some centres but not others. In a prospective study, we examined the influence of ultrasound guidance in embryo transfer performed on different days after oocyte retrieval. METHODS: Two different methods of embryo transfer were evaluated in 1069 consecutive transfers. The ultrasound-guided embryo transfer was used in 433 cases, whereas 636 embryo transfers were performed with the tactile assessment ('clinical feel') method. RESULTS: Ultrasound-guided embryo transfer yielded a higher overall pregnancy rate than the 'clinical feel' approach, 47 versus 36% (P < 0.001). This difference was statistically significant where embryos were transferred after 3 or 4 days of culture, 45.9 versus 37.1% (P = 0.001) and 42.3 versus 27% (P = 0.035) respectively but not significant (P = 0.112) on day 5 embryo transfer (56.3 versus 45.7%). Likewise, the implantation rate was significantly different between the two groups on day 3 and 4 embryo transfer, 23.3 versus 15.8% (P < 0.01) and 21.6 versus 15.7% (P < 0.05%) respectively but no statistical difference was noted on day 5 embryo transfer, 26.7 versus 23.6%. CONCLUSION: Ultrasound assistance in embryo transfer on day 3 and 4 significantly improved pregnancy rates in IVF but had no impact on day 5.     

Ultrasound-guided embryo transfer improves pregnancy rates and increases the frequency of easy transfers

BACKGROUND: Recent reports have suggested that ultrasound (US) guidance during embryo transfer might improve pregnancy rates. METHODS: A prospective randomized (computer-generated random table) trial was performed to compare embryo transfer under abdominal US guidance (n = 255 women) with clinical touch embryo transfer (n = 260). RESULTS: The clinical pregnancy rate was 26.3% (67/255) in the US-guided transfer group compared with 18.1% (47/260) in the clinical touch transfer group (P < 0.05). The implantation rate was 11.1% (100/903) in the US group compared with 7.5% (66/884) in the clinical touch group (P < 0.05). US-guided transfer was associated with a decrease in the difficulty of the transfers: 97% of transfers were easy in the US-guided group compared with 81% in the clinical touch group (P < 0.05). CONCLUSIONS: US-guided embryo transfer increased pregnancy and implantation rates in IVF cycles, as well as the frequency of easy transfers. It is suggested that the decrease in cervical and uterine trauma can play a role in the increase in pregnancy rates associated with US-guided transfer. It is recommended that embryo transfer should be performed under US guidance.     

Pregnancies following ovum donation in gonadal dysgenesis

Between February 1987 and February 1989, 13 women with primary ovarian failure due to gonadal dysgenesis were treated with embryo transfer following ovum donation in 22 cycles. Eight pregnancies were obtained (36.7% per transfer); four births of normal children, two spontaneous abortions and two other pregnancies currently ongoing (between 5 and 8 months). An association of percutaneous oestradiol, oestradiol valenate and intravaginal progesterone was used as hormone substitution and embryo transfer was only performed following assessment of the endometrium during a previous cycle. Apart from the day of embryo transfer, which was the same for all patients (the 2nd day after initiation of progesterone) various prognostic factors were analysed. These were the type of gonadal dysgenesis (45 XO, 46 XX or 46 XY), the number of embryos replaced, whether they had been frozen, whether the egg donor was anonymous and finally the influence of the hormone substitution protocol. Only the number of embryos replaced and the substitution protocol seemed to influence the implantation rate. The other parameters, and in particular the type of gonadal dysgenesis, seemed to have no effect on the results. The pregnancy rate per transfer was 30% for 45 XO (10 transfers), 25% for 46 XX (eight transfers) and 75% for 46 XY (four transfers).     

Luteal phase ovarian oestrogen is not essential for implantation and maintenance of pregnancy from surrogate embryo transfer in the rhesus monkey

The aim of this study was to investigate whether luteal phaseovarian oestrogen is required for blastocyst implantation andpregnancy maintenance in the rhesus monkey. Preimplantationembryos were retrieved from naturally ovulated, mated embryodonor monkeys. In group I, developmentally normal, age- andstage-matched embryos were transferred to recipient monkeysshowing naturally synchronized ovulatory cycles. Immediatelyprior to embryo transfer, recipients were subjected to bilateralovariectomy, and following transfer they were treated with i.m.injections of either progesterone (group Ia, n= 4), or oestradiol+ progesterone (group Ib, n= 2). Recipient monkeys of groupIc (n= 4) were subjected to sham ovariectomy and vehicle injection.In group Ia, progesterone supplementation alone led to threepregnancies and live births. In group Ib, there was one livebirth. In the control group Ic, four transfers resulted in twolive births and one abortion on cycle day 58. Analysis of serumprogesterone and oestradiol profiles showed that oestradiolhad declined to undetectable levels within 3–5 days afterovariectomy in group Ia recipients, and the area under the curveof serum oestrogen concentrations during the peri-implantationperiod (days 10–20 after ovulation) were less (p< 0.001)in group Ia compared with group Ic. There were no changes inthe area under the curve among serum progesterone concentrationsin all the subgroups. In group II, long-term ovariectomizedembryo recipients (n= 4) were primed with oestradiol till cycleday 11 of simulated transfer cycle, and received progesteronetreatment from cycle day 10 till the end of the experiment.Of four transfers, live births were recorded in two cases, whilein one case abortion occurred on cycle day 66. Serum oestradiolconcentrations were undetectable during the presumptive peri-implantationperiod of pregnancy cycles in group II recipient monkeys. Noyes‘dating of endometrial samples collected from both groups ondays 5–7 after the oestrogen rise revealed that endometrialhistology synchronized well with those found during days 3–5after ovulation in normal menstrual cycle. We conclude thatluteal phase ovarian oestrogen is not essential for progesterone-dependentendometrial receptivity and response leading to implantationand pregnancy maintenance in the rhesus monkey.     

Infertility: Ultrasonic monitoring during replacement of frozen/thawed embryos in natural and hormone replacement cycles

We evaluated the results of cryopreserved/thawed embryo replacement(FER) to determine if the outcome following transfer in a naturalcycle in a defined group was different to that from a hormonereplacement cycle, and also to assess vaginal ultrasonographicfeatures that assist in predicting the timing of the transfer.At the London Fertility Centre, 149 consecutive FER cycles werestudied retrospectively. Women with proven ovulation and regularcycles were included during natural cycles (n = 77). The hormonereplacement cycle group included women with anovulation, irregularcycles and older women (n = 72). In the natural cycle group,transfer was performed following positive urinary luteinizinghormone (LH) surge and confirmation of ovulation by ultrasonography.With the hormone replacement therapy group, gonadotrophin-releasinghormone analogue was used to induce pituitary down-regulation,oestradiol valerate was supplemented followed by regular ultrasoundmonitoring, and FER 2 days following the initiation of progesterone,which was started once adequate endometrial development wasnoticed on ultrasonography. The pregnancy and ongoing/deliveryrates were analysed in relation to the treatment cycle, age,number and quality of embryos transferred. Ultrasonographicfeatures were examined to evaluate their relationship with theoutcome of treatment. The results showed that no differenceexisted between natural and hormone replacement cycles in pregnancyrates per cycle (26 and 25%), ongoing/delivery rate (20.8% inboth groups), and implantation rate (10.3 and 10.6%). Pregnancyrates were not influenced by the number of embryos transferred,stage at which the embryos were cryopreserved, or whether theywere extra embryos from in-vitro fertilization/embryo transfer,or gamete intra-Fallopian transfer. The pregnancy rate was low(7.4%) if the embryos had less than three blastomeres and ifthe fragmentation was >50% (0% pregnancy rate). With hormonereplacement cycles, age did not influence the outcome, and women40 years and older had a pregnancy rate of 29.4% per cycle.No pregnancies resulted in the natural cycle group if the maximumfollicular diameter was > 22 mm before ovulation. When poorendometrial development was noted (thickness < 8 mm and gradeC) no pregnancy resulted from FER in natural or hormone replacementcycles. The pregnancy rates were higher when the endometriumwas 8 mm thickness and grade B (42.4%) or grade A (21.2%). Weconcluded that FER outcomes in natural cycles were similar tothose arising with hormone replacement therapy provided goodselection criteria were used, and vaginal ultrasonography canassist in timing the day of replacement and identify cases tobe cancelled before the transfer.     

Mid-cycle serum levels of endogenous LH are not associated with the likelihood of pregnancy in artificial frozen-thawed embryo transfer cycles without pituitary suppression

BACKGROUND: The aim of the present study was to evaluate the association between clinical pregnancy and serum luteinizing hormone (LH) levels, assessed after 14 days of endometrial preparation with estradiol (E(2)) in the absence of pituitary suppression during a frozen-thawed embryo transfer (FRET) cycle. METHODS: A total of 513 patients undergoing their first FRET cycle (01/99 to 11/05) participated in this prospective study. Endometrium preparation for FRET was started on cycle day 1 and continued for a fixed period of 14 days with trans-dermal E(2) patches. On day 14, serum LH, progesterone and E(2) levels were assessed. On day 15, progesterone supplementation was initiated and patients underwent embryo transfer on day 17 or day 18. The association between clinical pregnancy and LH levels was evaluated in groups of patients defined according to Tukey's Hinges percentile analysis of LH levels on day 14. In addition, robust logistic regression was performed with the dependent variable clinical pregnancy and independent variables LH, progesterone, embryos score, cycle rank and gravidity. RESULTS: Age, BMI, parity, cycle rank, embryo number, embryo score, endometrial diameter, E(2) and progesterone were not significantly different in cycles with low (0.1-8.1 IU/l; n = 132), intermediate (8.2-19.4 IU/l; n = 238) and high (20.0-78.0 IU/l; n = 143) levels of LH, respectively. Clinical pregnancy rates were not significantly different in cycles with low [12.1%, 95% confidence intervel (CI) 7.6-18.8], intermediate (13.4%, 9.7-18.4) and high levels of LH (16.1%, 11.0-23.0). Robust logistic regression analysis indicated that embryo score [Odds ratios (OR) 1.04, 95% CI 1.02-1.06, P < 0.01] was statistically significantly associated with the likelihood of clinical pregnancy achievement, but not day 14 levels of LH or progesterone, gravidity or cycle rank. CONCLUSIONS: The likelihood of clinical pregnancy is not associated with serum LH levels on day 14 of an artificial FRET cycle. Hormonal monitoring of LH levels does not yield useful information with regard to cycle management and patient prognosis, and should therefore not be conducted.     

Training of providers in embryo transfer: what is the minimum number of transfers required for proficiency?

BACKGROUND: Embryo transfer represents one of the most critical procedures in the practice of assisted reproduction. The objective of this study was to identify retrospectively the minimum number of embryo transfers required to train providers properly in this skill. METHODS AND RESULTS: The study group consisted of 204 patients who received embryo transfers between January 1996 and March 2000 in a university-based programme of assisted reproduction. The main outcome measure was clinical pregnancies per embryo transfer. Five Fellow trainees performed a total of 204 embryo transfers for an overall pregnancy rate of 45.5% per embryo transfer (93/204). In comparison, the programme pregnancy rate per transfer for experienced providers was 47.3% (560/1179). A chronological graph of each individual trainee's experience for the first 50 embryo transfers performed suggested a lower initial pregnancy rate for three of the five trainees. To determine whether a learning curve might exist, results of the first 25 transfers were compared as a subgroup with the second 25 transfers. Pregnancy rates were lower for the 1-25 transfer subgroup than in the 26-50 subgroup for three of the five Fellow trainees, although the difference was not statistically significant. CONCLUSION: Clinical pregnancy rates of Fellows-in-training were indistinguishable statistically from those of experienced staff by 50 transfers.     

Lack of placental protein 14 production in pregnancy after frozen embryo transfer, down-regulation of anterior pituitary and administration of exogenous oestradiol and progesterone

The circulating levels of placental protein 14 (PP14) and progesterone were measured in three pregnancies resulting from the transfer of cryopreserved embryos. Two of these women had suppressed ovarian activity as a result of pituitary down-regulation with the luteinizing hormone-releasing hormone agonist (buserelin) prior to treatment with exogenous oestradiol and progesterone. After 14 days of oral oestradiol treatment and if the endometrial thickness was greater than 7 mm, progesterone was given intramuscularly for a further 14 days with embryo transfer on the third day of this treatment. On confirmation of pregnancy by human chorionic gonadotrophin analysis, progesterone administration was altered to transvaginal pessaries for maintenance of adequate progesterone levels and endometrial support. In the two women with ovarian suppression, PP14 levels remained below the 2.5th centile of the normal range for pregnancy. In the third pregnancy, embryo transfer was performed 3 days after a spontaneous luteinizing hormone surge in a normal menstrual cycle. In this pregnancy, PP14 levels were within the normal range. Ultrasonic examination confirmed three normal ongoing singleton pregnancies. These results suggest that the majority of PP14 production in normal pregnancy is under ovarian or anterior pituitary control and that the influence of progesterone is of a secondary nature.     

A program of oocyte donation and gamete intra-Fallopian transfer

The outcome of a series of 19 patients with premature ovarianfailure (POF) undergoing gamete intra-Fallopian transfer (GIFT),utilizing donated oocytes, is described. The steroid replacementprotocol consisted of the administration of increasing dosagesof 17-oestradiol (E2) and progesterone (P4). Hormonal replacementwas maintained until day 100 of gestation. All patients underwentan evaluation cycle in which serum levels of E2 and P4 weremonitored and an endometrial biopsy was performed either 7 or11 days after initiation of progesterone administration. Allcases of GIFT were performed between days 12 and 15 of the inducedmenstrual cycle. Of the 19 patients treated, 11 became pregnant,giving a clinical pregnancy rate of 58% (visualization of gestationalsac by ultrasound). Two patients aborted between the 4th and5th weeks of gestation. No ectopic pregnancies occurred. Threeof the seven deliveries involved multiple births. Details ofthe circulating hormone levels and endometrial response arediscussed     

Ultrasound-guided soft catheter embryo transfers will improve pregnancy rates in in-vitro fertilization

Attempts to improve clinical pregnancy rates after in-vitro fertilization (IVF) and embryo transfer are constantly being made. Two changes in technique of embryo transfer of potential clinical importance were evaluated over two contiguous time periods in order to observe any corresponding change in clinical pregnancy (CP) rate per transfer: (i) embryo transfer catheter; (ii) ultrasound guidance. Catheter choices were hard: Tefcat, Tom Cat, or Norfolk; or soft: Frydman or Wallace. Ultrasound visualization was considered to be excellent/good when the catheter could be followed from the cervix to the fundus by transabdominal ultrasound with retention of the embryo-containing fluid droplet; fair/poor if visualization could not document the sequence of events. Embryo transfers were performed in 518 cycles. CP rates per transfer using soft and hard catheters was 36 and 17% (P < 0.000) respectively. CP rates per transfer for transfers performed with and without ultrasound guidance were 38 and 25% (P < 0.002) respectively. A statistically significant difference was also noted when visualization ranks were compared. CP rates per transfer in all excellent/good ultrasound-guided transfers was 41.5 versus 16.7% for fair/poor transfers (P < 0.038). In conclusion, performance of embryo transfer with a soft catheter under ultrasound guidance with good visualization resulted in a significant increase in clinical pregnancy rates.     

IVF-ET新鲜周期移植不孕而冷冻周期妊娠的相关因素分析

目的探讨IVF-ET助孕治疗中新鲜周期移植不孕而后续的冷冻周期成功妊娠的原因以指导治疗。方法回顾性分析体外受精或单精子卵母细胞浆内注射-胚胎移植术（IVF/ICSI-ET）治疗患者950个周期,其中新鲜周期妊娠组780个周期和新鲜周期未孕冷冻周期妊娠组170个周期,比较两组患者年龄、不孕年限、病因及基础FSH水平、Gn使用情况、hCG日内膜、激素水平、卵泡数、获卵及胚胎情况的差异。采用单因素分析筛选出差异有统计学意义的因素进行多因素分析。结果经Logistic回归分析得出hCG日P4、hCG日E2/1000是妊娠的独立影响因素。hCG日P4（OR=1.653,P=0.015,95%CI：1.101～2.482）,hCG日E2/1000（OR=1.219,P=0.001,95%CI：1.085～1.369）。hCG日酮孕每增加1ng/ml,新鲜周期不孕而冷冻周期妊娠的风险将增加1.653倍。hCG日E2每增加1000pg/ml,新鲜周期不孕而冷冻周期妊娠的风险将增加1.219倍。结论 hCG日的P4和E2是导致新鲜移植不孕而冷冻周期妊娠的重要原因。P4和E2过高,可考虑放弃新鲜移植,采用冷冻移植。     

Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme

BACKGROUND: Data on the effect of elective single embryo transfer (eSET) on the total and multiple pregnancy rates of an IVF/ICSI programme are reported. METHODS AND RESULTS: A retrospective cohort analysis of eSET was carried out over a 4 year period. A total of 1559 cycles resulted in 1464 transfers; 299 transfers of one top quality embryo (20.4%) and 86 of one non-top quality embryo (5.9%) yielded 149 conceptions (49.8%) with 105 ongoing pregnancies (35.1%) and 26 conceptions (30.2%) with 19 ongoing implantations (22.1%) respectively; 1079 transfers of two (n = 853; 58.3%) or more than two (n = 226; 15.4%) embryos yielded 366 ongoing pregnancies (33.9%). The ongoing pregnancy rates for the years between 1998 and 2001 were 35.9, 27.9, 31.9 and 31.0% per oocyte retrieval and 38.5, 29.4, 34.1 and 33.2% per transfer. There were no differences in pregnancy rates between any of the years. The average ongoing pregnancy rate (>12 weeks) over the 4 years was 31.5% per started cycle and 33.5% per transfer; the average number of embryos transferred decreased from 2.26 (1998) to 1.79 (2001); the multiple pregnancy and twinning rates dropped from 33.6 and 29.5% (1998) to 18.6 and 16.3% (2001) respectively. CONCLUSIONS: Judicious application of eSET can halve the twinning rate while maintaining the overall pregnancy rate.     

胚胎解冻移植周期移植日和移植后3天血清雌孕激素水平对临床结局的影响

目的探讨胚胎解冻移植周期血E2、P及其比值与自然周期解冻移植结局的关系。方法对北京大学第三医院自2008年1月至2008年10月自然周期方案行胚胎解冻移植的742个周期进行总结分析。根据移植后的临床结局分为妊娠组（331例,又分宫内活胎组及妊娠结局不良组）及未妊娠组（411例）,分别于移植当日及移植后3天取血查血清雌二醇（E2）和孕激素（P）。结果本组解冻移植后临床妊娠率为33．42％;移植后妊娠与否与是否发生卵泡黄素化无关,P〉0．05;宫内活胎组移植日P／E2值为117．6±71．5,移植后3天的E2、P、P／E2分别为628．2±329．4,90．6±61．8,及161．2±104．9,明显低于未妊娠组,P〈0．05。结论自然周期胚胎解冻移植当日及移植后3天周期恰当的雌孕激素比例与胚胎解冻移植临床结局有关。     

Nurses performing embryo transfer: the development and results of the Birmingham experience

Although in-vitro fertilization treatment is doctor-led, many of its steps are performed by nurses. The embryo transfer step, however, is performed exclusively by doctors in the majority of units. In our unit, doctors performed embryo transfers from June 1994 until December 1995 (period I). From January 1996 until May 1997 (period II) the nurses, after appropriate training, performed the procedure. When they experienced difficulties during the mock transfer performed immediately before the real transfer, or if they were not available to do the procedure, a doctor performed it. In period I, 488 embryo transfers were performed (all by doctors), with a pregnancy rate per transfer of 35% and an implantation rate of 16%. In period II, 522 embryo transfers were performed. Nurses performed 371 (71%) and doctors 151 (29%) of the procedures. The pregnancy rate per nurse-transfer was 40.2% and per doctor-transfer 41%. The corresponding implantation rates were 16.9% and 17%. None of these differences were statistically significant (P > 0.05). These data indicate that, with appropriate training and medical back-up, nurses can perform the majority of embryo transfers with ease and outcome comparable to that of doctor embryo transfer.      

Embryos cultured in vitro with multinucleated blastomeres have poor implantation potential in human in-vitro fertilization and intracytoplasmic sperm injection

The aim of the present study was to investigate pregnancy rates ensuing from transfer of embryos with multinucleated blastomeres. In our in- vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programme, 1735 embryo transfers were performed from January 1, 1995 to August 31, 1996. In 136 of these transfers at least one embryo with one or more multinucleated blastomeres was present per transfer (study group). For each of these 136 transfers, two matched controls with transfer of exclusively mononucleated embryos were selected (control group). Matching was carried out according to age, method of fertilization (IVF or ICSI), number of transferred embryos and quality score of transferred embryos. In the study group, there were eight transfers of exclusively multinucleated embryos from which one pregnancy ensued and 128 transfers in which multinucleated and mononucleated embryos were transferred together leading to 23 pregnancies. The overall clinical pregnancy rate per transfer was 16.9% in the study group versus 28.7% in the control group (P = 0.01). The ongoing pregnancy rate per transfer was 13.2% in the study group versus 23.2% in the control group (P = 0.03). The implantation rate per transferred embryo was 6.0% in the study group versus 11.3% in the control group (P = 0.003). This study shows that embryos with one or more multinucleated blastomeres have a poorer implantation potential than embryos with mononucleated blastomeres. Transfer of embryos with multinucleated blastomeres should hence only be considered when insufficient numbers of embryos with only mononucleated blastomeres are present.      

GnRH antagonists followed by a decline in serum estradiol results in adverse outcomes in donor oocyte cycles

BACKGROUND: The aim of this retrospective study was to assess clinical outcomes using GnRH antagonists in oocyte donation cycles. METHODS: Between July 2000 and June 2001, 40 recipient cycles generated from donor oocytes were evaluated. Controlled ovarian hyperstimulation (COH) was started on cycle day 2 using recombinant gonadotrophins (225 IU daily). GnRH antagonist was started on cycle day 6 of COH. All recipients were synchronized to donors using GnRH agonist followed by estrogen and progesterone supplementation. Main outcome measures were days of stimulation (DOS), number of ampoules used, peak serum estradiol, number of oocytes, fertilization rate, embryo score, clinical on-going pregnancy rate and implantation rate. RESULTS: Thirty-seven donor cycles (93%) underwent oocyte retrieval, resulting in 36 embryo transfers. Fourteen cycles (35%) had decreased serum estradiol after initiation of GnRH antagonist. No differences were seen in numbers of FSH ampoules, DOS, peak serum estradiol, number of retrieved oocytes, fertilization rate and embryo quality. However, clinical pregnancy rate per initiated cycle [14% (2/14) versus 54% (14/26)], ongoing pregnancy rate per initiated cycle [7% (1/14) versus 46% (12/26)] and implantation rate (4 versus 24%) were all significantly less (P <0.05) following a decrease in serum estradiol after initiation of GnRH antagonist. No clinical predictor, including donor age, basal day 2 FSH or estradiol, ovarian morphology or serum estradiol prior to GnRH antagonist, was predictive of a decline in serum estradiol following GnRH antagonist. CONCLUSION: These data demonstrate an adverse effect on clinical outcome in cycles, resulting in a decline in serum estradiol after GnRH antagonist administration. This effect was unpredictable and provided a simplified protocol for oocyte donation cycles; nonetheless, further study is needed to clarify the adverse effects of GnRH antagonists in oocyte donation cycles.     

Ultrasound measurement of the uterocervical angle before embryo transfer: a prospective controlled study

BACKGROUND: The study aim was to determine whether moulding the embryo transfer catheter according to the uterocervical angle measured by ultrasound could improve pregnancy and implantation rates. METHODS: Patients were alternately allocated to one of two groups. In the ultrasound-guided group (n = 320), the catheter was moulded according to the uterocervical angle measured by abdominal ultrasound. In controls (n = 320), embryo transfer was performed using the "clinical feel" method. RESULTS: Moulding the embryo transfer catheter according to the uterocervical angle significantly increased clinical pregnancy [(OR = 1.57, 95% CI (1.08-2.27)] and implantation rates [(OR = 1.47, 95% CI (1.10-1.96)] compared with the "clinical feel" method. It also significantly reduced difficult transfers [(OR = 0.25, 95% CI (0.16-0.40)] and blood during transfers [OR = 0.71, 95% CI (0.50-0.99)]. Patients with large angles (>60 degrees ) had significantly lower pregnancy rates compared with those with no angle [OR = 0.36, 95% CI (0.16-0.52)]. CONCLUSIONS: Moulding the embryo transfer catheter according to the uterocervical angle measured by ultrasound increases clinical pregnancy and implantation rates and diminishes the incidence of difficult and bloody transfers.     

Controlled preparation of the endometrium with exogenous oestradiol and progesterone: a novel regimen not using a gonadotrophin-releasing hormone agonist.

In women having inactive ovaries, controlled preparation of the endometrium has been achieved with exogenous oestradiol and progesterone. We report on the feasibility and practicality of using a similar regimen for timing transfers of cryopreserved embryos in women whose ovaries have not been suppressed. A total of 91 women having cryopreserved embryos from previous in-vitro fertilization (IVF) attempts received 4 mg/day of oestradiol valerate, starting on cycle day 1 of spontaneous (n = 85) or induced (n = 6) menstruation. A single blood sample was obtained on cycle day 14 for the measurement of plasma progesterone, oestradiol and luteinizing hormone (LH). Vaginal administration of micronized progesterone (300 mg/day) was started on day 15. Cryopreserved embryos were transferred on day 17 or 18 provided that day 14 plasma progesterone remained < or = 0.5 ng/ml, thereby confirming the absence of spontaneous ovulation prior to the administration of exogenous progesterone. Out of 91 cycles studied, plasma progesterone was found to be elevated (> 1 ng/ml) in only three (3.2%). Of the 88 scheduled transfers, 31 did not take place because no embryo survived thawing. In the remaining 57 cycles, 116 embryos were transferred resulting in 10 pregnancies, giving pregnancy and embryo implantation rates of 17.5 and 8.6% respectively. When a positive beta human chorionic gonadotrophin (HCG) titre was obtained, supplementation with oral oestradiol and vaginal progesterone was continued until placental autonomy was achieved. Of the 10 pregnancies, five (50%) were lost during the first trimester (biochemical, n = 1; miscarriage, n = 3; ectopic, n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)