Replacement Of Frozen-thawed Embryos Research Articles

When Should We Freeze Embryos? Current Data for Fresh and Frozen Embryo Replacement IVF Cycles.

Recent years have seen a dramatic rise in the number of frozen-thawed embryo replacement (FER) cycles. Along with the advances in embryo cryopreservation techniques, the optimization of endometrial receptivity has resulted in outcomes for FER that are similar to fresh embryo transfer. However, the question of whether the Freeze all strategy is for all is nowadays a hot topic. This review addresses this issue and describes current evidence based on randomized controlled trials and observational studies. To date, it is reasonable to perform FER in cases with a clear indication for the benefits of such strategy including impending ovarian hyperstimulation syndrome (OHSS) or preimplantation genetic testing for aneuploidy (PGT-A); however, this strategy does not fit for all. This review analyses the pros and cons of the freeze all strategy highlighting the need to follow a personalized plan in embryo transfer, avoiding a freeze all methodology for all patients in an unselected manner.

A UK-wide cross-sectional survey of practice exploring current trends in endometrial preparation for frozen-thawed embryo replacement

In the United Kingdom, between 2012 and 2017 the annual number of frozen-thawed embryo replacement (FER) cycles doubled, while fresh cycles declined. With FER now accounting for 34% of IVF cycles, the aim of this UK-wide survey of IVF clinics was to determine current trends in the management of FER. A senior clinician in each of the 84 UK IVF clinics was asked to complete an online survey between September 2018 and February 2019 focussing on their clinic’s first-line protocols for FER. Sixty-five clinics (77%) responded, accounting for approximately 24,419 FER cycles annually. In ovulatory women, 69% of clinics favour medicated, 26% natural cycle and 5% modified natural cycle FER. In medicated FER, 61% of clinics undertake blastocyst transfer on the sixth day of progesterone administration, 21% on the fifth, 13% on the seventh, 3% on the fourth and 2% on the third. The preferred route of progesterone in medicated FER is vaginal, favoured by 82% of clinics. For pituitary suppression, 55% of clinics favour GnRH-agonist, 11% GnRH-antagonist and 34% oestrogen-only. In natural cycle FER, 31% always, 44% sometimes and 25% never give supplementary luteal support. In summary, the results illustrate wide variation in practice and highlight key research priorities.

The role of frozen–thawed embryo replacement cycles in assisted conception

Key content Recent years have seen a dramatic rise in the number of frozen–thawed embryo replacement (FER) cycles. Improved embryo cryopreservation techniques have resulted in outcomes for FER that are similar to fresh embryo transfer. FER maximises the cumulative live‐birth rate of a fresh in vitro fertilisation (IVF) cycle by using excess embryos and encourages a policy of single embryo transfer; this has contributed to a fall in the multiple pregnancy rate associated with IVF. Freezing all suitable embryos in a fresh cycle reduces the risk of ovarian hyperstimulation syndrome. The endometrium is prepared for FER by a natural or medicated protocol; the optimum method is unknown. Learning objectives To appreciate the importance of FER in IVF practice. To understand the current debate surrounding fresh versus frozen IVF. To understand the indications for, and methods of, embryo cryopreservation. To understand the commonly used methods of endometrial preparation for FER. To be able to date an FER pregnancy. Ethical issues Funding from the National Health Service (NHS) for embryo storage and FER varies widely across the UK; where funding is limited, this can result in viable embryos being discarded. When an embryo is created by a couple, the consent of both partners is required before transferring the embryo.

Frozen-thawed embryo replacement (FER): a UK-wide survey of IVF clinics demonstrating wide variation in practice and a comparison of GnRH-antagonist with GnRH-agonist pituitary suppression in medicated FER

Frozen-thawed embryo replacement (FER): a UK-wide survey of IVF clinics demonstrating wide variation in practice and a comparison of GnRH-antagonist with GnRH-agonist pituitary suppression in medicated FER

Embryo quality before and after slow freezing: Viability, implantation and pregnancy rates in 627 single frozen-thawed embryo replacement cycles following failure of fresh transfer

Frozen embryo transfer cycles are now common practice, however, various aspects regarding the potential of frozen embryos remain unclear. The main goal of the present study was to assess embryo quality before and after slow freezing procedure, and more specifically blastomere loss and embryo quality as indicator of viability. A single center retrospective analysis of single frozen-thawed embryo replacements (s-FER) was performed. The embryo quality before and after slow freezing and thawing, implantation, and pregnancy rates were recorded. One hundred and twenty seven s-FER were included in the final analysis. The probability of achieving an ongoing pregnancy was significantly associated with embryo quality and the percentage of blastomere loss after thawing. Considering thawed embryos, a non-significant difference in term of implantation rate was observed, regardless to their post-thawing quality and the percentage of blastomeres loss. In conclusion, current data suggest that thawed embryos are capable of implantation regardless of their morphological quality and the degree of cryoinjury sustained.

Randomized, controlled pilot trial of natural versus hormone replacement therapy cycles in frozen embryo replacement in vitro fertilization

To determine whether there is any difference between the outcomes of two standard treatment protocols for frozen embryo replacement (FER): natural and down-regulated hormone replacement treatment (HRT). Open, single-center, randomized, controlled pilot trial. Private fertility clinic. Women (n = 159) planning an FER cycle at the Oxford Fertility Unit, aged <40 years at the time their embryos were frozen; with at least one blastocyst or two cleavage-stage embryos in storage; regular ovulatory cycles; and at most two previous FER cycles. Eligible participants were recruited and randomized between March 2010 and July 2012 into one of two standard FER treatment groups: natural (n = 80) menstrual (Natural) or GnRH agonist/HRT (n = 79) cycles. Live birth rate after replacement of frozen-thawed embryos, clinical pregnancy rate, implantation rate, and cycle cancellations. A total of 159 women were randomized (80 Natural; 79 HRT), and 145 had ET and completed the study (72 Natural; 73 HRT). Pregnancy outcomes were not significantly different between the two groups. The live birth rates were 26.3% (Natural) and 31.7% (HRT) per randomized patient. Per ET/protocol the live birth rates were 29.2% and 34.2%. The implantation rates were 24.3% and 26.0%, and there were three twin births in the Natural and five in the HRT arms. The findings of this pilot study support the suggestion that for women with ovulatory cycles undergoing FER, the outcomes are similar between natural and HRT protocols. NCT00843570. Registered at www.clinicaltrials.gov.

Endometrial receptivity under hormone replacement therapy in oocyte-donation recipient patients: transcriptomic approach

Purpose: Few studies have investigated the endometrial receptivity status of oocyte-donation (OD) recipient patients at the specific hormone replacement therapy (HRT)-cycle timing (5 to 6 days after progesterone administration) where embryos at blastocyst stage were mostly replaced. The aim of our study was to analyse, during the implantation window, (i) the global endometrial gene expression profile, and (ii) the endometrial receptivity exploration by the Win-Test® in OD recipient patients under HRT compared to spontaneous cycle in patients awaiting for IVF.Material and methods: This study included OD recipient patients without (n=7) or with (OD RIF, n=20) repeated implantation failures and 12 normal responder patients in spontaneous cycles used as control. Endometrial biopsies were performed during the peri-implantation phase. Samples were analysed using DNA microarrays and the endometrial gene expression profiles of HRT-treated OD recipient patients and of patients in spontaneous cycles were compared. Then, specific biomarkers of endometrial receptivity were assessed in the two groups of HRT-treated OD patients in comparison to control patientsResults: The global gene expression profile of peri-implantation endometrial samples from HRT-treated OD recipients and from patients in spontaneous cycles was different with significant alterations in the oestrogen receptor signalling [GTF2H2B, POLR2B, POLR2E], VEGF family ligand-receptor interactions [VEGFR1, VEGFB] and integrin signalling [ITGAL, PAK7, ILK]. Using specific biomarkers of human endometrial receptivity, we found that endometrium was non-receptive (29 % and 43 % in OD and RIF OD patients, respectively) or partially receptive (71 and 43 % in OD and RIF OD patients, respectively), at Pg+5/+6, in majority of HRT-treated patients. In OD RIF patients, a delay of the implantation window was observed. However, by targeting personalized embryos transfer by identifying for each patient the HRT-cycle day where endometrium is receptive, with respect of the synchronization of embryo-endometrium dialogue, high pregnancy rate per frozen-thawed embryo replacement (50%) was obtained in OD RIF patients.Conclusion: This study underlines the need to take into account the individual patient’s response to HRT cycles and to move to a patient-tailored care management.

Assisted reproductive technology in Egypt, 2003–2004: Results generated from the Egyptian IVF registry

Abstract Objective To summarize the results of ART procedures cycles initiated in Egypt during the years 2003–2004. Design The forms, prepared by the International Committee Monitoring Assisted Reproductive Technologies (ICMART), were distributed to all IVF centers in Egypt. Participants All IVF centers in Egypt were invited to voluntarily participate. Main outcome measures The total number of standard IVF, ICSI, FET after standard IVF and ICSI cycles, incidence of clinical pregnancy, abortion, delivery, stillbirth and complications rates. Results Data were anonymously received from 18 centers in 2003 and 15 centers in 2004, with a total of 16,862 reported cycles. ICSI constituted 91.9%; frozen-thawed embryo replacement cycles represented 7.0%, while IVF constituted only 1.0% of the total number of ART cycles. For ICSI, the clinical pregnancy rates per aspiration and per transfer were 38% and 42%, respectively. The distribution of singleton, twin, triplet and high-order deliveries for IVF, ICSI and FET combined was 62.5, 21.8, and 2.4, respectively. This gives a total multiple delivery rates of 24.2%. As a result of ART activities, 2656 neonates were reported born. Complications of ART were mainly ovarian hyperstimulation syndrome, complicating 1.75% of cycles; the occurrence of bleeding in 0.4% and infection in 0.03% of all aspiration cycles. Conclusions These are the fourth and fifth consecutive reports of the activities of the Egyptian IVF registry for cycles initiated during the years 2003–2004. The clinical pregnancy rates were comparable with the previous reports. The multiple pregnancy rate is still higher than would be desired, as a result of the proportion of women receiving high number of embryos (⩾3 embryos) per transfer. OHSS is also high and therefore preventative measures must be stricter. More efforts are needed to complete data on deliveries and perinatal mortalities.

Low-dose human chorionic gonadotropin versus estradiol/progesterone luteal phase support in gonadotropin-releasing hormone agonist–triggered assisted reproductive technique cycles: understanding a new approach

It remains unclear how GnRH agonist (GnRHa) triggering affects the luteal phase, so we investigated the luteal phase after GnRHa triggering, supported with conventional E(2)/P with or without low-dose hCG. E(2)/P support, compared with low-dose hCG, induced a shorter luteal phase (11.2 ± 1.1 vs. 15.0 ± 1.6 days) and fewer subjective complaints (0 vs. 42%), whereas hCG caused more free fluid accumulation and enlarged ovaries than E(2)/P alone. Steroids and low-dose hCG differentially affected corpus luteum function, ovarian size, free fluid accumulation, and patient comfort.

A Bahraini Registry of Assisted Reproductive Technology for Period of 2000–2006: Hoping to Stave off Reporting Stalemate

Objective To report the first Bahrain national registry for ART treatments initiated from January 1, 2000 to December 31, 2005. Methods The “World Report on ART” forms, prepared by the International Committee for Monitoring Assisted Reproductive Technology (ICMART), were filled from database records of all procedures and their respective outcome carried out at Banoon ART Centre, the Military Hospital, Bahrain during the period of 2000-2006. Results A total of 1 490 completed cycles were performed. ICSI constituted 42.68% (636), IVF constituted 35.50% (529), while frozen-thawed embryo replacement cycles represented only 21.18% (325) of all ART cycles. The clinical pregnancy rates per transfer for IVF and ICSI cycles were 26.65% and 21.70%, respectively. The distribution of singleton, twin and triplet deliveries for IVF, ICSI and FET combined were 80.0%, 16.3% and 3.7%, respectively. The average delivery rate per clinical pregnancy for fresh and frozen cycles was 57.3%. As a result of ART services, 266 neonates were born. Complications of ART were solely due to ovarian hyperstimulation syndrome (OHSS) which constituted 2.26% of all aspirated cycles. Conclusion Multiple pregnancy rate was high due to transferring >3 embryos. Pregnancy loss and OHSS were relatively high thus preventative measures were recommended. This report paves the way for the other IVF centers in Bahrain to provide their own data for the national ART registry.

New frontiers of assisted reproductive technology (Chien Tien Hsu Memorial Lecture 2007)

Many significant advances have been made in assisted reproductive technology since the birth of the first baby conceived with in vitro fertilization and embryo transfer. The development of recombinant gonadotropins and gonadotropin releasing hormone antagonists helps to simplify the ovarian stimulation. Excessive ovarian stimulation should be avoided because of the risks of ovarian hyperstimulation syndrome and reduction in endometrial receptivity. Maturation of oocytes in vitro has been developed in some centers. It is still uncertain whether techniques such as assisted hatching, blastocyst transfer and pre-implantation aneuploidy screening can improve the live birth rates in assisted reproduction. The introduction of pre-implantation genetic diagnosis for selection of human lymphocyte antigens (HLA) compatible embryos for treatment of siblings has raised ethical concerns. There is a higher risk of obstetric complications and congenital abnormalities even in singleton pregnancies achieved with assisted reproduction. Because of the risks of multiple pregnancies, elective single embryo transfer is increasingly used in good-prognosis patients. With a good freezing program, the cumulative pregnancy rate (including the pregnancies from subsequent replacement of frozen-thawed embryos) is not adversely affected. Improvement in cryopreservation techniques has made it possible to cryopreserve slices of ovarian tissue or oocytes, thus helping women who have to receive sterilizing forms of anti-cancer treatment to preserve their fertility. It is important that the development of the new techniques should be based on good scientific evidence. Ethical, legal and social implications should also be considered before the introduction of new techniques.

Viability of frozen-thawed human embryos with one–two blastomeres lysis

To assess the impact of one-two blastomeres lysis on the viability of thawed day 3 human embryos. A retrospective analysis was performed on 248 frozen-thawed embryo replacement cycles in which all embryos were frozen at day 3 at the seven-eight cell stage with <or=10% fragmentation. Outcomes of transfer cycles with fully intact embryos (intact group) were compared with those in which all transferred embryos have lost one-two blastomeres (damage group). Comparable pregnancy rates (38.46% vs 38.64%), birth rates (34.62% vs 36.36%) and implantation rates (26.31% vs 26.25%) were obtained in intact and damage groups. These results were also not significantly different from mixed transfer cycles in which one intact embryo and one damaged embryo were transferred together. The developmental potential of partially damaged cryopreserved human embryos with less than 25% cells loss is comparable to that of fully intact embryos. Presence of one-two lysed blastomeres in the thawed day 3 embryo does not appear to have a negative influence on the further development of the sibling intact cells.

The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles

To examine the relationship between endometrial thickness and outcome of medicated frozen-thawed embryo replacement (FER) cycles. A retrospective observational study. Assisted conception unit at a university hospital. All patients who underwent an FER cycle between 1997 and April 2006 and met the inclusion criteria. For endometrial preparation, a daily dose of 6 mg of oral E(2) valerate was started on menstrual day 1, and P pessaries (800 mg daily) were administrated when the endometrial thickness had reached 7 mm or more, with ET taking place 2-3 days later. The FER cycles were categorized according to endometrial thickness measurement on the day of P supplementation. Implantation, clinical pregnancy, ongoing pregnancy, and live birth rates. In all, 768 consecutive medicated FER cycles were analyzed. The lowest pregnancy rates were associated with endometrial thickness <7 mm (n = 13) and >14 mm (n = 12; 7% in both groups). Significantly higher implantation (19% vs. 12%), clinical pregnancy (30% vs. 18%), ongoing pregnancy (27% vs. 16%), and live birth (25% vs. 14%) rates were achieved in cycles where endometrial thickness was 9-14 mm (n = 386), compared with those in which endometrial thickness was 7-8 mm (n = 357). These differences remained significant after adjusting for confounding variables (adjusted odds ratio [OR] = 1.83 [confidence interval {CI} = 1.3-2.6] for clinical pregnancy, 1.8 [CI = 1.2-2.6] for ongoing pregnancy and 1.9 [CI = 1.3-2.8] for live birth). In medicated FER cycles, an endometrial thickness of 9-14 mm measured on the day of P supplementation is associated with higher implantation and pregnancy rates compared with an endometrial thickness of 7-8 mm.

Triggering of final oocyte maturation with gonadotropin-releasing hormone agonist or human chorionic gonadotropin. Live birth after frozen-thawed embryo replacement cycles

To report the outcome of frozen-thawed embryo replacement cycles after GnRH-agonist triggering of final oocyte maturation in the collecting cycle with GnRH-antagonist. Prospective, observational, multicentric clinical study. Tertiary university-affiliated IVF centers. Patients under observation previously had been recruited into two concurrently performed, independent, randomized controlled trials (comparing hCG with GnRH-agonist for triggering final oocyte maturation in GnRH-antagonist multiple-dose protocols in normal responder patients) encompassing a total of 228 participants. Surplus embryos or oocytes at the pronuclear stage were cryopreserved in 53 patients after hCG administration and 32 patients after GnRH-agonist administration on the basis of patient choice, pronuclear/embryo availability, and local laws. Transfer of frozen-thawed embryos. Live birth rate. Thirty-one and 23 patients after administration of hCG and GnRH-agonist, respectively, started a frozen-embryo replacement cycle by September 2005, with 25 and 16 patients eventually undergoing at least one frozen-thawed ET. Live birth rate per ET was 18.5% (95% confidence interval [CI], 8.2-36.7) and 30.0% (95% CI, 14.5-51.9) after hCG and GnRH-agonist triggering, respectively. Cumulative live birth rate per patient starting a frozen-embryo replacement cycle was 16.1% (95% CI, 7.1-32.6) and 26.1% (95% CI, 12.5-46.5) for hCG and GnRH-agonist, respectively. The likelihood of live birth in frozen-embryo replacement cycles after GnRH-agonist triggering of final oocyte maturation does not appear to be impaired.

A Comparison of Psychological Functioning in Couples Undergoing Frozen–Thawed Embryo Replacement in Various Stages of Treatment Using the Mean Affect Adjective Check List (MAACL)

The objectives were to identify the stage(s) of frozen embryo replacement cycle where the couples are most vulnerable to psychological dysfunction. Assessment was performed by using the Mean Affect Adjective Check-List (MAACL). Thirty couples completed the MAACL questionnaire at the following stages: (a) pretreatment (visit 1), (b) before embryo transfer (visit 2), and (c) before pregnancy test (visit 3). Each partner had to complete a separate questionnaire set. For both partners, the depression score for visit 3 was significantly higher and the sensation seeking and positive affect scores were significantly lower than the corresponding scores for earlier visits. Anxiety scores were similar for all visits. For men, the hostility scores were significantly higher between visits 1 and 2 while in women the same was reported between visits 3 and 2. Psychological counselling should be targeted at couples especially after embryo transfer. MAACL is a useful method for measuring psychological dysfunction in these couples.

Comparison of pregnancy outcome of pronuclear- and multicellular-stage frozen-thawed embryo transfers.

Our purpose was to determine if supernumerary embryos generated by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) should be frozen (using 1,2-propanediol) at the pronuclear or multicellular stage. The study was a retrospective analysis conducted at the Dubai Gynaecology & Fertility Centre of the Department of Health & Medical Services, Dubai, U.A.E. One hundred forty-one women undergoing frozen-thawed embryo replacement cycles with IVF generated embryos and 84 women undergoing the same with ICSI generated embryos. Supernumerary, IVF-generated embryos frozen at the multicellular stage had a significantly higher rate of survival on thawing (73.9%) than embryos frozen at the pronuclear stage (64.4%). The morphological grades of the embryos in the two groups were similar, but a significantly higher pregnancy rate was obtained with embryos frozen at the multicellular stage (22.8%) than with pronuclear-stage embryos (14.8%). Similarly, with ICSI-generated embryos, significantly higher survival was seen with multicellular-stage frozen embryos (74.8%) than pronuclear-stage embryos (64.4%). The morphological grades of the embryos and pregnancy outcomes of the two groups were similar. Supernumerary embryos generated by IVF and ICSI should be frozen at the multicellular stage so as to allow selection of the best embryos for transfer and embryo freezing of only robust embryos.

Obstetric outcome of 904 pregnancies after intracytoplasmic sperm injection.

The obstetric data of 904 consecutive pregnancies obtained after intracytoplasmic sperm injection (ICSI) using ejaculated spermatozoa (group I), epididymal spermatozoa (group II), testicular spermatozoa (group III) and after the replacement of frozen-thawed embryos (group IV) are described. In all, there were 785 pregnancies in group I, 37 pregnancies in group II, 30 pregnancies in group III and 52 pregnancies in group IV. A total of 24 pregnancies (2.5%) have so far been lost to follow-up. The incidence of pregnancy loss, i.e. subclinical pregnancies, clinical abortions and ectopic pregnancies were highest in group IV (61.4%). Early pregnancy loss in groups I, II and III were 21.9, 37.8 and 33.3% respectively. Prenatal diagnosis was performed in 64.4% of the clinical pregnancies: amniocentesis in 48.2% and chorionic villus sampling in 16.2%. The karyotypes were normal in 97.6% of the prenatal diagnoses and there were 1.2% de novo and 1.2% inherited chromosome aberrations. Pregnancy complications such as prematurity and low birthweight were related to pregnancy multiplicity. Perinatal mortality occurred in 15 babies (17.1 per thousand), including nine intrauterine fetal deaths after 25 weeks of gestation and six cases of mortality during the first 7 days after birth. There is no evidence that the technique of ICSI using sperm cells of different origins yielded a higher obstetric risk.

Microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection: a new effective approach to infertility as a result of congenital bilateral absence of the vas deferens

To present and assess the efficacy of a new approach for the treatment of infertility due to congenital bilateral absence of the vas deferens. A retrospective study of consecutive trials. Centre for Reproductive Medicine, which is a tertiary referral institution. Twelve couples suffering from infertility because of congenital bilateral absence of the vas deferens. A microsurgical epididymal sperm aspiration procedure was performed in the husbands, followed by intracytoplasmic sperm injection of oocytes recovered from the wives. Cleaving embryos were transferred to the uterine cavity 48 hours after the intracytoplasmic sperm injection procedure. Sperm parameters after microsurgical epididymal sperm aspiration, fertilization, cleavage, and pregnancy rates. In all 14 microsurgical epididymal sperm aspiration procedures, sperm was retrieved. Notwithstanding the poor quality of this epididymal sperm, a fertilization rate of 58% was achieved after intracytoplasmic sperm injection. On 10 occasions, embryos were transferred and five patients became pregnant, i.e., an overall pregnancy rate of 35.7% per started trial and 50.0% per transfer. Another two patients became pregnant after replacement of frozen-thawed embryos, which increases the pregnancy rate to 50.0% per microsurgical epididymal sperm aspiration procedure. Early pregnancy wastage was 57%, limiting the ongoing pregnancy rate to 21.4% per microsurgical epididymal sperm aspiration procedure. This study shows the combined microsurgical epididymal sperm aspiration-intracytoplasmic sperm injection procedure to be highly efficient in achieving fertilization in vitro, even after recovery of grossly impaired epididymal sperm.

Partial dissection of the zona pellucida of frozen-thawed e human embryos may enhance blastocyst hatching, implantation, and pregnancy rates

The rate of successful implantation after replacement of frozen-thawed embryos in in vitro fertilization is commonly only 5% to 10% per embryo. A limiting factor may be inability of otherwise viable embryos to be released from the intact zonae pellucidae. Culture conditions and/or cryopreservation in in vitro fertilization may affect the zona and impair blastocyst hatching. Therefore opening of the zona by partial slicing by means of micromanipulation before replacement of early cleaved embryos may improve chances of eventual hatching (referred to as assisted hatching). In 65 thawed embryo replacement cycles methyl-prednisolone and antibiotics were given for 4 days mid cycle. Assisted hatching was performed in 32 cycles, with 33 cycles left as controls. Patient's age, infertility, cycle supplementation, and number of thawed and replaced embryos did not differ significantly between the two groups. Rates of viable embryonic implantation were 16% (10/63) and 9% (6/64) in the assisted hatching and control groups, respectively. Group sizes need approximately to double before this trend toward improved implantation with the use of assisted hatching reaches statistical significance.

Replacement of frozen - thawed embryos in artificial and natural cycles: A prospective semi-randomized study

This prospective partly-randomized study assessed the relative efficacy of two strategies of patient management for the replacement of frozen-thawed embryos. A luteinizing hormone-releasing hormone (LHRH) agonist was used to induce a temporary hypogonadism in a group of patients who were then prepared for implantation by endometrial priming with hormone replacement therapy (HRT): oral oestradiol valerate and then oestradiol valerate and injections of progesterone. A second group of patients had their frozen-thawed embryos replaced during their natural cycles. Of the 84 patients treated with the LHRH regimen, 80 had embryos replaced and 16 (20%) clinical pregnancies were established. Of the 78 patients treated with natural cycles, 70 had embryos replaced and 14 (20%) achieved clinical pregnancies. There were no statistical differences between the two groups in terms of age, obstetric history, duration of infertility, number of oocytes retrieved and fertilized or the number of embryos frozen following ovarian stimulation in the embryo 'generating' cycle. In terms of pregnancy rates, both protocols were equally effective. However, the LHRH-HRT protocol was of great value in the management of oligomenorrhoeic patients and in establishing standard conditions for implantation in cyclic patients.