ICSI increases ongoing pregnancy rates in patients with poor response cycle: multivariate analysis of 2819 cycles

The objective of this study was to evaluate the prognosis of patients with a first treatment cycle that was defined as a poor ovarian response cycle according to the new ESHRE consensus criteria. The first documented cycle of poor response for a patient and all the cycles that followed were retrospectively analysed. Factors that were associated with ongoing pregnancy rates were assessed using multivariate analysis. In total, this study evaluated 1014 patients that underwent 2819 consecutive IVF cycles. As expected, patients with poor response cycles were older and had less oocytes retrieved and less embryos transferred. Multivariate analysis for ongoing pregnancy rates adjusted for patient and the cycle characteristics revealed that the intracytoplasmic sperm injection (ICSI) procedure was associated with a significant increase of 40% in ongoing pregnancy rate (adjusted success ratio 1.40, 95% CI 1.00–1.96). Age over 41 years and additional cycles with poor response, were associated with significantly less ongoing pregnancy rate. However, the cumulative pregnancy rates were 29.5% and 36.4% following five and seven cycles, respectively. In conclusion, performing ICSI may improve the ongoing pregnancy rates in poor responders. Further studies are needed to establish the number of cycles recommended in these patients.Patients with poor ovarian response cycles are currently the most challenging group of fertility patients. We are yet far from understanding the factors which cause reduced ovarian response and further away from finding a solution to this painful problem. In this work, we present that with current available treatment modalities, the results can be improved. We show that performing intracytoplasmic sperm injection and implementation of additional number of treatment cycles may improve the ongoing pregnancy rates of patients with a first treatment cycle that is defined as a poor ovarian response cycle. In addition, we investigated the cumulative pregnancy rates in this group and the effect of performing a number of treatment cycles.     

Preparation of endometrium for frozen embryo replacement cycles: a systematic review and meta-analysis

Purpose

The purpose of this study was to evaluate the best protocol to prepare endometrium for frozen embryo replacement (FER) cycles.

Methods

This study is a systematic review and meta-analysis. Following PubMed and OvidSP search, a total of 1166 studies published after 1990 were identified following removal of duplicates. Following exclusion of studies not matching our inclusion criteria, a total of 33 studies were analyzed. Primary outcome measure was live birth. The following protocols, including true natural cycle (tNC), modified natural cycle (mNC), artificial cycle (AC) with or without suppression, and mild ovarian stimulation (OS) with gonadotropin (Gn) or aromatase inhibitor (AI), were compared.

Results

No statistically significant difference for both clinical pregnancy and live birth was noted between tNC and mNC groups. When tNC and AC without suppression groups are compared, there was a statistically significant difference in clinical pregnancy rate in favor of tNC, whereas it failed to reach statistical significance for live birth. When tNC and AC with suppression groups are compared, there was a statistically significant difference in live birth rate favoring the latter. Similar pregnancy outcome was noted among mNC versus AC with or without suppression groups. Similarly, no difference in clinical pregnancy and live birth was noted when ACs with or without suppression groups are compared.

Conclusions

There is no consistent superiority of any endometrial preparation for FER. However, mNC has several advantages (being patient-friendly; yielding at least equivalent or better pregnancy rates when compared with tNC and AC with or without suppression; may not require LPS). Mild OS with Gn or AI may be promising.

     

Effect of blastomere loss on the outcome of frozen embryo replacement cycles

OBJECTIVE: To assess the impact of survival of cryopreservation and thawing with all blastomeres intact on the outcome of frozen embryo replacement (FER) cycles. DESIGN: Prospective observational study. SETTING: University-affiliated tertiary referral assisted conception unit. PATIENT(S): The number of intact blastomeres before cryopreservation and after thawing was prospectively recorded in 1,687 cleavage-stage embryos thawed in 377 FER cycles. The cycles were categorized into two groups: group A (n = 184) included cycles in which all embryos transferred survived the cryopreservation and thawing process with all their original blastomeres intact; group B (n = 193) included cycles in which embryos transferred included at least one partially damaged embryo that has lost up to 50% of its original blastomere number. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy and embryo implantation rates. RESULT(S): Groups A and B were comparable with respect to mean age at cryopreservation, mean number of oocytes retrieved and fertilized normally in the fresh cycle, and mean age at frozen transfer. No significant difference was found between the two groups with regard to mean number of frozen and thawed embryos per cycle and mean endometrial thickness reached before P supplementation. More embryos were transferred per cycle in group B than group A (2.4 +/- 0.6 vs. 2.1 +/- 0.6, respectively). However, the pregnancy and clinical pregnancy rates per cycle were significantly higher in group A than in group B (39.1% and 28.3% vs. 22.8% and 13.5%, respectively). The implantation rate was also higher in group A than in group B (17.3% vs. 8.1%, respectively). CONCLUSION(S): FER cycles in which all embryos transferred remained fully intact at thawing achieve a better outcome than those with at least one partially damaged embryo.     

Expected poor ovarian response in predicting cumulative pregnancy rates: a powerful tool

Poor ovarian response in IVF cycles is associated with poor pregnancy rates. Expected poor responders may represent the worst prognostic group. Data were used from 222 patients starting the first of three IVF treatment cycles. The predictability of ongoing pregnancy after three cycles was analysed using survival analysis and hazard rate ratios. If first cycle poor responders were also predicted to have a poor response, they were classified as expected poor responders. The predicted pregnancy rate in cycles 2 and 3 for women with an observed poor response in the first cycle was approximately 24% for women aged 30 years and approximately 14% for women aged 40 years. For women with an expected poor response these rates were 12% and 6%, respectively. In contrast, women aged 40 years with an unexpected poor response still had a predicted cumulative pregnancy rate of 24%. Age as a sole predictor of cumulative pregnancy does not help to identify poor prognosis cases. Cumulative pregnancy rates in subsequent cycles for patients with an observed poor response in the first cycle may be a reason to refrain from further treatment. However, if such poor response has been expected, further treatment may be avoided because of an unfavourable prognosis for pregnancy.     

To transfer fresh or thawed embryos?

Worldwide freezing and thawing of embryos has been increasingly used since the first infant was born as a result of this technique in 1984. The use of frozen embryo replacement (FER) currently even exceeds the number of fresh cycles performed in some countries. This article discusses the pros and cons of FER versus fresh-embryo transfer with regard to both single-cycle and cumulative pregnancy and delivery rates. The review discusses the obvious advantages of FER: minimizing the proportion of pharmacological and surgical treatments, and lowering the risk of ovarian hyperstimulation syndrome and multiple pregnancies, thereby increasing the safety for mother and child. Finally the article describes the accumulating literature on perinatal and long-term child outcome after transfer of frozen/thawed embryos, including a discussion on the concerns regarding cryo techniques and their possible roles in the subsequent development of fetus and child. Because larger and more detailed data sets are available for early cleavage-stage embryo freezing and slow freezing, they are the main focus of this review.     

Trophoblast deportation and the maternal inflammatory response in pre-eclampsia

We have proposed that the maternal syndrome of pre-eclampsia is caused by a systemic inflammatory response involving both leucocytes and endothelium. This inflammatory response is present also in normal pregnancy, but in a milder form. The inflammatory stimulus is most likely to come from the placenta. Syncytiotrophoblast apoptotic debris, which is shed into the maternal circulation in normal pregnancy and in increased amounts in pre-eclampsia, may be the stimulus for this response. It may also contribute to the suppression of Th1 responses seen in pregnancy.     

Performance of patients with a "frozen pelvis" in an in vitro fertilization program

It is now possible to identify and study the performance of different subgroups of patients in in vitro fertilization (IVF) programs. Patients with severe pelvic adhesions due to pelvic inflammatory disease (PID) or endometriosis were classed as having a frozen pelvis if less than or equal to 20% of total ovarian surface was visible and if the rest of the ovary was bound down with significant adhesions. IVF offers the only hope of pregnancy for these patients. Fifty-one treatment cycles in 23 such patients were matched against 51 cycles in 48 patients with adhesion-free ovaries. The study group had a significantly higher number of cancelled oocyte retrievals because of poor estradiol (E2) response. They also had a significantly lower rate of E2 rise and a lower peak value of E2 before and after the administration of human chorionic gonadotropin. These patients took longer to respond to a hyperstimulation regime, and when a response occurred they formed fewer follicles, as measured with the use of ultrasound. Lower numbers of oocytes were obtained from this group, but the fertilization rate of oocytes was the same for both groups. One pregnancy occurred in the study group and 11 in the control group. It is possible that disruption of ovarian blood supply or mechanical factors due to the pressure of significant adhesions prevent a good follicular response in patients with a frozen pelvis.     

Transfer of embryos into the uterus: How much do technical factors affect pregnancy rates?

Objective Our objective was to identify the effect on outcome of (a) ultrasound-assisted embryo transfer, (b) the use of different embryo transfer catheters, and (c) the length of time the patients remain in the supine position after embryo transfer.Setting The setting was a private fertility center.Subjects This was a prospective study of 178 in vitro fertilization and embryo transfers (IVF-ET) and 63 frozen embryo replacements (FER).Results The pregnancy rate was 28.7% following IVF-ET and 31.8% for FER. Ultrasound-assisted transfer did not affect the outcome (29 vs 30.3%). There was no difference in the performance of the Wallace and Frydman catheters with regard to outcome (30.3 vs 30.7%). Although there was an increase in pregnancy rate as the time interval in the supine position after ET increased, this needs a larger study.Conclusion The parameter studies did not affect the outcome of IVF/ET or FER. Some factors encouraged us to recommend ultrasound-assisted transfer in some cases, and the use of a Frydman catheter for transfer and to encourage the supine position after transfer for longer periods.     

Previous abortion is a positive predictor for ongoing pregnancy in the next cycle in women with repeated IVF failures

Early pregnancy loss is common among women treated with assisted reproduction treatment, but whether it is a prognostic factor for success in subsequent IVF cycles is not well established. The aim of this study was to determine whether a biochemical pregnancy (BP) or spontaneous abortion (SA) affects the pregnancy rates in the following cycle. A retrospective study of 2687 women undergoing 6678 cycles between January 1998 and March 2010 was performed. Ongoing pregnancy rate (PR) per cycle was compared between patients with a pregnancy loss versus a negative β-HCG in their previous cycles. Multivariate analysis of factors affecting ongoing pregnancy rate was performed. BP and/or SA in the first three cycles did not significantly alter the chances to conceive (16.9% patients with BP and/or SA in the previous cycle versus 16.5% patients with no previous pregnancy). From cycle 4 onwards, the presence of a previous abortion (either BP or SA) was associated with better ongoing PR (23.0% versus 11.2%, P < 0.001). In conclusion, BP and/or SA in a previous cycle appears to be a positive marker for success in subsequent cycles in patients with repeated IVF failures. These results should be further investigated in this challenging group of patients.Pregnancy loss in the first trimester is common among women treated with assisted reproduction treatment, but its significance regarding chances of future ongoing pregnancies is not well established. The aim of this study was to determine whether an early pregnancy loss during an IVF cycle, affects the ongoing pregnancy rates in following IVF cycles. A retrospective study of 2687 women undergoing 6678 IVF cycles between January 1998 and March 2010 was performed. Ongoing pregnancy rate was compared between patients with a pregnancy loss in their previous IVF cycle versus patients who failed to conceive (negative-human chorionic gonadotrophin blood test) in their previous IVF cycle. A multivariate analysis of factors affecting ongoing pregnancy rate including age, number of embryos transferred and aetiology of infertility was performed. We found that early pregnancy loss during the first three IVF cycles did not significantly alter the chances to conceive (pregnancy rates: 16.9% for patients with early pregnancy loss in the previous cycle compared to 16.5% in patients who didn’t conceive in the previous cycle). From cycle 4 onwards, the presence of a previous early pregnancy loss was associated with better ongoing pregnancy rate (23.0% compared to 11.2%, P < 0.001). In conclusion, early pregnancy loss in the previous cycle appears to be a positive marker for success in subsequent cycles in patients with repeated IVF failures.     

Effects of cryopreservation on testicular sperm nuclear DNA fragmentation and its relationship with assisted conception outcome following ICSI with testicular spermatozoa

The objective of the study was to investigate the effects of freeze-thawing on testicular sperm DNA fragmentation, fertilization rates and pregnancy rates following intracytoplasmic sperm injection with testicular spermatozoa (TESE). This ongoing prospective study included 88 couples attending for infertility treatment where the man presented with obstructive azoospermia at the Regional Fertility Centre, Belfast, UK. Patients were allocated to receive TESE treatment with fresh or freeze-thawed spermatozoa. Sperm aliquots were stored in liquid nitrogen at -196 degrees C following static phase vapour cooling or cooling at controlled rates using a programmable freezer. Samples were thawed at either room temperature or 37 degrees C. Sperm nuclear DNA; assessed by the alkaline Comet assay, was significantly damaged by slow freezing followed by fast thawing. Pregnancies were more likely to be achieved with spermatozoa displaying markedly less DNA damage. However, no differences were observed in the fertilization rates, the number of blastomeres or the cumulative embryo score between TESE cycles using either fresh or frozen thawed testicular spermatozoa. The pregnancy rates tended to be higher following fresh TESE cycles (30%) compared with TESE cycles using frozen-thawed testicular spermatozoa (26%), although this difference did not reach statistical significance. It is concluded that cryopreservation of testicular spermatozoa may reduce pregnancy rates, although this will only be confirmed by a much larger multi-centre trial.     

The total pregnancy potential per oocyte aspiration after assisted reproduction—in how many cycles are biologically competent oocytes available?

Purpose

While stimulation of women prior to assisted reproduction is associated with increased success rates, the total biological pregnancy potential per stimulation cycle is rarely assessed.

Methods

Retrospective sequential cohort study of the cumulative live birth rate in 1148 first IVF/ICSI-cycles and 5-year follow up of frozen embryo replacement (FER) cycles were used. Oocyte number, number of embryos transferred, and cryopreserved/thawed and transferred embryos in a FER cycle were registered for all patients. Children per oocyte and per transferred embryo and percentage of cycles with births were calculated.

Results

We obtained 9529 oocytes. Embryos (2507) were transferred in either fresh or FER cycles, resulting in 422 births and 474 live born children. Median age of the women was 32.5 years (range 20–41.5 years). In total, 34.3 % of all cycles ended with a live birth while in 65.7 % of the cycles, no oocytes were capable of developing into a child. The average number of oocytes needed per live born child after transfer of fresh and thawed embryos was 20 as only 5.0 % of oocytes aspirated in the first IVF/ICSI cycle had the competence to develop into a child.

Conclusions

In our setting, overall 5.0 % of the oocytes in a first cycle were biologically competent and in around 2/3 of all cycles, none of the oocytes had the potential to result in the birth of a child.

     

Ovarian activity during follicular-phase down regulation in in vitro fertilization is associated with advanced maternal age and a high recurrence rate in subsequent cycles

Purpose Previous reports have suggested that the ovarian response to leuprolide acetate is predictive of in vitro fertilization pregnancy rates. This study evaluated the outcome of in vitro fertilization cycles complicated by elevated estradiol levels during leuprolide acetate down regulation and the outcome of subsequent cycles in the same patients.Methods Two hundred fifty-two in vitro fertilization cycles were initiated utilizing leuprolide acetate down regulation beginning on cycle day 1.Results Seventy-four of these cycles had an elevated estradiol level at the time of the baseline scan (28%). This group of patients had a higher maternal age, a higher cycle cancellation rate (27.5 vs 16.3%), and a high rate of recurrence on subsequent cycles (63%).Conclusions The pregnancy rate per retrieval was equivalent in the two groups. This suggests that patients with advanced maternal age or a history of failure to suppress in a previous cycle may benefit from alternate regimens of superovulation.     

Retrospective analysis of 1217 IVF cycles in women aged 40 years and older

Older women comprise an increasing portion of patients entering assisted reproduction programmes. This study is a retrospective summary of the files of all patients aged 40 years and older at advent of IVF, between 1995 and 2004, in the authors' centre. In all, 381 women underwent 1217 initiated treatment cycles. Embryo transfer was performed in 62.6% of initiated cycles. Success rates declined with each year after age 40; pregnancy and delivery rates were 13.9 and 9.1% at age 40 and 2.8 and 0.7% at age 45. There were no deliveries at an older age. Logistic regression analysis showed the following factors were independently and significantly related to higher pregnancy rates: younger age, lower dose of gonadotrophins, greater number of mature follicles, endometrial thickness, and number of embryos transferred; prior pregnancy did not influence success. Retrieving more than four oocytes increased pregnancy rates in all women over 40. Transferring 3 embryos or more increased pregnancy rates in all ages, but reached statistical significance only in women aged 40-41 (P < 0.000). It is concluded that in women between 40 and 41 years of age, ovarian response is a major determinant of success, but not in women older than that. Unrealistic expectations may be avoided if accurate data are provided regarding delivery rates per year after age 40.     

Is laparoscopy necessary before assisted reproductive technology?

PURPOSE OF REVIEW: Laparoscopy is widely used during infertility work-up, although it is sometimes unnecessary. This review highlights when laparoscopic intervention should be used in women undergoing assisted reproductive technology cycles. RECENT FINDINGS: There is no evidence for an increase in pregnancy rates in assisted reproductive technology cycles following surgical treatment of pelvic adhesions or endometriosis with laparoscopy. If the patient has bilateral visible hydrosalpinges, laparoscopy may be an option for evaluation of the tubes and treatment with salpingectomy in order to enhance the chance of pregnancy before commencing an assisted reproductive technology cycle. Laparoscopic ovarian drilling before assisted reproductive technology may be considered a therapeutic option in polycystic ovary disease patients who previously had severe ovarian hyperstimulation syndrome. Finally, laparoscopy may be useful in replacing the transposed ovaries to their original sites in the pelvic cavity in previously treated cancer patients so that monitoring of the controlled ovarian hyperstimulation and the oocyte aspiration would be much easier during the assisted reproductive technology cycles. SUMMARY: Laparoscopy should be considered before assisted reproductive technology cycles if the procedure diagnoses and treats a pelvic pathology at the same time and if laparoscopic intervention increases the chance of pregnancy following these cycles.     

Serum HCG measured in the peri-implantation period predicts IVF cycle outcomes

The current study assessed the relationship between serum concentrations of human chorionic gonadotrophin (HCG) measured in the peri-implantation period and various outcome measures following blastocyst transfer in IVF cycles. The study group included 767 autologous IVF cycles, each with the transfer of two fresh blastocysts in a 6-year study period, ending 31 December 2009. Outcome measures were ectopic pregnancy, biochemical pregnancy loss, ongoing pregnancy, spontaneous abortion and multiple pregnancy. Peri-implantation serum HCG concentration measured 5 days after blastocyst transfer was highly predictive of these outcome measures. These findings suggest embryonic implantation and developmental fate are largely determined by 5 days after blastocyst transfer and that very early serum HCG measurements may be useful markers of IVF outcome.     

The effect of multiple cycles in oocyte donors

OBJECTIVE: The purpose of this study was to determine whether multiple controlled ovarian hyperstimulation cycles in oocyte donors affect the ovarian response, the oocytes retrieved, or the pregnancy rates. STUDY DESIGN: A retrospective chart review of repeat donor in vitro fertilization cycles between 1992 and 2003 at the University of Cincinnati Center for Reproductive Health was performed. The variables that were examined included the peak estradiol level, the length of stimulation, the number of follicles >15 mm, the amount of gonadotropins that were used, the number of oocytes that were retrieved and inseminated, the average number of cells per embryo at the time of transfer, and the clinical pregnancy rates. RESULTS: A total of 107 in vitro fertilized donor oocyte cycles were analyzed, of which 45 young healthy women underwent at least 2 cycles and 17 women underwent 3 cycles. Donors who underwent a second or third cycle demonstrated no differences in the cycle parameters that were observed. CONCLUSION: Repeated controlled ovarian hyperstimulation cycles in a donor population does not demonstrate a diminished ovarian response to exogenous gonadotropins. Oocyte donors can undergo up to 3 stimulation cycles without a negative affect on the ovarian response to gonadotropins, the number of mature oocytes retrieved, the embryo quality, or the clinical pregnancy rate.     

An Updated Review of Ectopic Pregnancies Resulting from Assisted Reproduction

Purpose of Review

The purpose of this study was to review the most recent data regarding clinical risk factors for ectopic pregnancy (EP) among patients pursuing assisted reproduction, and the diagnosis and management of EP in this specific population.

Recent Findings

EP rates following assisted reproduction have fallen over time to 1–2%, identical to the general population. Clinical risk factors for EP following assisted reproduction include the transfer of autologous, fresh and cleavage-stage embryos. Use of a GnRH agonist trigger alone for fresh cycles is associated with a greater risk of EP than hCG trigger. Serial hCG measurements and transvaginal ultrasound remain the mainstay of EP diagnosis. The addition of endometrial sampling to exclude failing intrauterine pregnancy spares a majority of patients unnecessary methotrexate. Two recent meta-analyses confirm that methotrexate for EP does not diminish subsequent response to controlled ovarian hyperstimulation (COH), while data conflict regarding the effects of salpingectomy on subsequent ovarian response. A recent randomized controlled trial, primarily in a non-infertility population, showed similar rates of subsequent intrauterine pregnancy following salpingectomy or salpingostomy in the presence of normal contralateral fallopian tubes. A large population-based study confirmed this finding, but reported higher ongoing pregnancy rates following tubal preservation in patients with infertility or tubal disease attempting natural conception.

Summary

The risk of EP following IVF appears largely mediated by altered endometrial receptivity, shown to result from COH and GnRH agonist-only triggers. Transfer of frozen-thawed blastocysts confers the lowest rate of EP following IVF. Methotrexate does not impact subsequent ovarian response to stimulation, though the effects of salpingectomy remain to be determined. Salpingectomy and salpingostomy confer equitable subsequent ongoing pregnancy rates, though tubal preservation may confer an advantage in women with tubal disease or infertility planning natural conception.

     

Natural-cycle in vitro fertilization in women aged over 44 years.

Women who are 44 years of age or more are usually denied infertility treatment because of their low response to ovarian stimulation and the extremely low pregnancy rate that can be achieved. The object of this study was to assess the place of natural-cycle in vitro fertilization (IVF) in this population. From January 1996 to September 1997, all consecutive women aged 44-47 years who approached our unit seeking infertility treatment with their own oocytes were enrolled in the study. After a counselling session in which the advantage of egg donation was discussed, women who still wished to try to conceive by utilizing their own oocytes were treated according to the following protocol. Ultrasound and hormonal surveillance was carried out starting 5 days prior to the presumed ovulation day, based on previous menstrual history. Ovum pick-up was timed either by detection of the luteinizing hormone surge or by human chorionic gonadotropin administration. In total, 48 treatment cycles were conducted in 20 women. Oocyte retrieval was successful in 22 cycles. Fertilization and cleavage rates of 48% and 100%, respectively, were detected. Nine of the 12 embryos transferred were defined as grade A. One chemical and one ongoing pregnancy were achieved. We conclude that, despite the fact that high-quality embryos can be obtained in this population, the likelihood of pregnancy is low.     

Frozen embryo transfer outcome according to reason for freezing the embryos

PURPOSE: To determine if cryopreservation influences pregnancy outcome following transfer. METHODS: Retrospective cohort analyses of frozen embryo transfer (ET) cycles divided into five different categories according to reason for freezing. RESULTS: Frozen embryos remaining as a result of failing to conceive with the previous fresh transfer or those remaining because of cancellation of fresh ET related to inadequate endometrial thickness, result in lower pregnancy rates (PRs). CONCLUSIONS: The fact that embryos never deselected in a group whose fresh ET was canceled because of risk of ovarian hyperstimulation did not have the best results suggests that these oocytes may not be of equal quality to those attained with a more modest response.     

Subcutaneous estradiol pellets for endometrial preparation in donor oocyte recipients with a poor endometrial response

Purpose: The purpose of this study was to evaluate the clinical effectiveness of subcutaneous estradiol pellets in donor oocyte recipients with an inadequate endometrial response. Methods: The subjects were 13 women with ovarian failure and a maximal endometrial thickness <10 mm on standard estrogen regimens, as demonstrated during mock and/or prior oocyte donation cycles. They underwent pellet implantation (100–250 mg of estradiol) 6–13 weeks before oocyte donation. Results: Maximal (mean ± SD) endometrial thickness was 8.7±1.5 mm on standard regimens, in contrast to 11.7± 1.8 mm on pellets, while estradiol levels were 674±844 and 815±706 pg/ml, respectively. The estradiol:estrone ratio on pellets was >1. There was 1 pregnancy with early loss during 10 cycles on other estrogen regimens and 12 pregnancies during 19 cycles on pellets. The pregnancy and implantation rates were, respectively, 63 and 27% on pellets and 41 and 14% on standard regimens in historical controls. Conclusions: We conclude that estradiol pellets after a single administration provide constant estradiol levels extending into the first trimester of pregnancy, a physiologic estradiol:estrone ratio, and a better endometrial response than standard estrogen regimens. Implantation and pregnancy rates are higher. This approach may be especially suitable for recipients with a poor endometrial response. Presented at the IXth World Congress on In Vitro Fertilization and Assisted Reproduction, Vienna, Austria, April 3, 1995, and the 51st Annual Meeting of the American Society for Reproductive Medicine, Seattle, Washington, October 7–12, 1995.