Subsequent Embryo Transfer Research Articles

Two protocols to treat thin endometrium with granulocyte colony-stimulating factor during frozen embryo transfer cycles

The efficacy of two granulocyte colony-stimulating factor (G-CSF) protocols for thin endometrium were investigated. Eighty-two patients were diagnosed with thin endometrium (<7 mm). Thirty patients with previously cancelled embryo transfers received intrauterine G-CSF in subsequent frozen embryo transfer (FET) cycles. Patients were divided into the G-CSF only and G-CSF with endometrial scratch subgroups. Compared with previous cycles, endometrial thickness increased from 5.7 ± 0.7 mm to 8.1 ± 2.1 mm after G-CSF treatment (P < 0.001). Endometrial thickness increases were not significantly different between the two subgroups. The G-CSF with endometrial scratch subgroup established nominally higher though non-significant clinical pregnancy and live birth rates than the G-CSF only subgroup (53.8 % versus 42.9% and 38.5% versus 28.6%, respectively). Fifty-two patients underwent FET despite edometrial thickness less than 7 mm, and were included as controls. Significantly higher embryo implantation and clinical pregnancy rates were observed in the G-CSF group compared with the control group (31.5% versus 13.9%; P < 0.01; 48.1% versus 25.0%; P = 0.038, respectively). Endometrial scracth did not impair G-CSF treatment for thin endometrium and favoured pregnancy and live birth rates. For patients with thin endometrium, embryo transfer cancellation and G-CSF treatment in subsequent FET cycles is beneficial.

Early Parkinson's disease symptoms in -synuclein transgenic monkeys

Parkinson's disease (PD) is an age-dependent neurodegenerative disease that can be caused by genetic mutations in α-synuclein (α-syn) or duplication of wild-type α-syn; PD is characterized by the deposition of α-syn aggregates, indicating a gain of toxicity from accumulation of α-syn. Although the major neuropathologic feature of PD is the degeneration of dopaminergic (DA) neurons in the substantia nigra, non-motor symptoms including anxiety, cognitive defect and sleep disorder precede the onset of motor impairment, and many clinical symptoms of PD are not caused by degeneration of DA neurons. Non-human primate models of PD are important for revealing the early pathology in PD and identifying effective treatments. We established transgenic PD rhesus monkeys that express mutant α-syn (A53T). Six transgenic A53T monkeys were produced via lentiviral vector expressing A53T in fertilized monkey eggs and subsequent embryo transfer to surrogates. Transgenic A53T is expressed in the monkey brain and causes age-dependent non-motor symptoms, including cognitive defects and anxiety phenotype, without detectable sleeping disorders. The transgenic α-syn monkeys demonstrate the specific early symptoms caused by mutant α-syn and provide insight into treatment of early PD.

The clinical outcomes of day 3 4-cell embryos after extended in vitro culture.

To evaluate the development potential and clinical significance of day 3 4-cell embryos after extended in vitro culture. This study was a retrospective cohort study for patients with infertility treatment between January 2011 and July 2013. Patients undergoing blastocyst culture in controlled ovarian hyperstimulation cycles using surplus embryos were analyzed in the study. A total of 764 women undergoing blastocyst culture with 1,522 surplus 4-cell embryos on day 3 were analyzed. An additional 2,391 patients with embryos undergoing blastocyst culture during the same period with embryos having more blastomeres were chosen as control. After extended culture, 253 embryos from 183 cycles in the study group which developed to blastocysts were frozen, and 118 embryos were warmed in subsequent frozen embryo transfer cycles. Implantation rates, clinical pregnancy rates (PRs) and ongoing PRs were 33.3 %, 38.4 % and 31.4 %, respectively, which were similar to those of the control group. The singleton birth weights of newborns using these blastocysts showed no significant difference to that seen in the control group. Surplus 4-cell embryos on day 3 displayed lower blastulation rates. However, once a blastocyst is obtained, it has equivalent clinical outcomes. Embryos that are developmentally lagging on day 3 can be observed in extended culture to increase the cumulative chances of a successful pregnancy.

Elective cryopreservation of all embryos and subsequent cryothaw embryo transfer results in better outcomes than fresh embryo transfer in shared egg donor program

To compare if cryopreservation of all embryos and subsequent cryothawe embryo transfer (ET) results in better outcomes compared with fresh ET in shared egg donor program and recipients. Open randomized controlled trial. From November 2012 to March 2013, 100 women from shared egg donor program that were submitted to oocyte retrieval were selected. The inclusion criteria were: age between 21 and 34 years-old, number of retrieved oocytes between 10 and 20, normal karyotype, no signs of endometriosis, no severe male factor and normal ovarian reserve. Each women shared half of their oocytes with a recipient. In the day of oocyte retrieval, the women were allocated in two groups. In group one, all the embryos were cryopreserved in day 5 and 2 blastocysts transferred in a subsequent cycle. In group two, 2 blastocysts were transferred in the same cycle. The exclusion criterion was less than two blastocysts five days after oocyte retrieval. Recipients that received fresh embryos from both groups were included as a third group. All recipients transferred 2 blastocysts in day 5. The outcomes were clinical pregnancy rate, implantation rate, miscarriage rate and multiple pregnancy rate. The comparisons among the three groups were performed two by two using chi-square test. Egg donors with fresh ET presented significantly lower clinical pregnancy rate (50%, n=47) than egg donors with frozen ET (72%, n= 50) or recipients (70.1%,n= 9; p=0.026 and 0.049, respectively). The implantation rate were also significantly lower in this group (28%) than frozen ET group (42%; p=0.042) and lower but not significantly than recipients group (39%, p=0.064). There was no differences comparing these outcomes between donors that cryopreserved embryos and recipients. No differences in miscarriage or multiple pregnancy rates was demonstrated among the groups. Three donors with fresh embryo transfer presented ovarian hyperstimulation syndrome. In shared egg donors, cryopreservation of all embryos with cryothaw transfer in subsequent cycle improves clinical pregnancy and implantation rate comparing to donors with fresh embryo transfer. In shared egg program, the policy of frozen all embryos seems to be a good choice.

High normal CGG repeat number on the fragile x mental retardation 1 (FMR1) gene is not correlated with diminished ovarian reserve

OBJECTIVE: Inversions are structural chromosome abnormalities that are associated with infertility due to the increased risk of producing unbalanced gametes from recombination events within the inverted chromosome segment. However, there is also evidence indicating the presence of an inter-chromosomal effect during chromosome segregation influencing the generation of other chromosome aneuploidies. The aim of this study was to evaluate the nature of chromosome errors in IVF blastocysts from carriers of balanced chromosome inversions. DESIGN: Research study. MATERIALS AND METHODS: Infertility patients with balanced chromosome inversions (n1⁄430; female carriers1⁄420, male carriers1⁄410) and maternal age-matched infertile controls with normal karyotypes that concurrently cycled (n1⁄430), consented with IRB approval to an IVF cycle with comprehensive chromosome screening (CCS). All embryos were cultured to the blastocyst stage with a trophectoderm biopsy performed for CCS using SNP microarray (RMA-NJ). Only euploid or balanced blastocysts were transferred in a subsequent frozen embryo transfer. Statistical analysis of aneuploidy and outcome data was performed using a two sided Fisher’s exact test with p value of 0.05 for significance. RESULTS: Maternal ovarian reserve, paternal age, oocytes retrieved, fertilization rate and the number of blastocysts biopsied were comparable between the two groups. The chromosomes that contained the balanced inversions varied but were mostly the larger chromosomes including 1, 2, 3, 5, 7, 9 and 17. The incidence of aneuploidy, excluding the chromosome with the inversion, was significantly higher for the inversion patients compared to the maternal age matched controls (Inversion1⁄459% vs. Control1⁄449%; P<0.001). However, following transfer of a euploid blastocyst there was an equivalent live birth rate (Inversion1⁄473.7% vs. Control1⁄478.3%; ns). CONCLUSION: Carriers of balanced chromosome inversions exhibited higher aneuploidy rates for chromosomes that were not involved in the inversion compared to maternal age-matched controls, signifying the occurrence of an inter-chromosomal effect. However, despite a higher aneuploidy rate, carriers of balanced inversions experienced excellent ART outcomes following the transfer of euploid blastocysts. These results provide valuable information for clinical management of infertility patients carrying balanced inversions prior to infertility treatment.

Preimplantation genetic screening (PGS) with vitrification reduces miscarriage and improves cumulative live birth compared to unscreened frozen embryos

Goals of IVF include achieving a viable pregnancy and live birth of a healthy baby as quickly and efficiently as possible. This study analyzes cumulative live-birth outcomes with and without PGS and array comparative hybridization (aCGH) in patients where blastocysts were frozen and then thawed in subsequent frozen embryo transfers (FET) cycles.

Efficacy of cryopreservation of embryos generated by intracytoplasmic sperm injection with spermatozoa from frozen testicular tissue.

To evaluate the viability of frozen embryos generated by intracytoplasmic sperm injection (ICSI) with frozen testicular spermatozoa. A total of 68 fresh embryo transfer (ET) cycles and 85 subsequent frozen-thawed ET (FET) cycles were grouped according to the source of spermatozoa: fresh testicular spermatozoa (TESE) or frozen-thawed testicular spermatozoa (t-TESE). There were no significant differences in the age of female patients, number of oocytes, or fertilization rates in fresh ET cycles with TESE (TESE-fresh ET) versus t-TESE (t-TESE-fresh ET). The rate of embryo survival after thawing (95.7 % vs. 94.0 %) was similar in frozen ET cycles (FET) with TESE (TESE-FET) and with t-TESE (t-TESE-FET). While there were significant differences in the proportion of good quality embryos, no statistical differences were found in the pregnancy or clinical abortion rates between the two groups. Moreover, delivery rates were not significantly different. Although the proportion of good quality embryos was affected by cryopreservation of testicular tissue, embryo survival rate was not. As well, subsequent pregnancy could be achieved successfully via t-TESE-FET cycles. Therefore, FET is not affected by the cryopreservation of testicular tissue, and avoids further oocyte retrieval and TESE procedures.

Role of baseline antral follicle count and anti-Mullerian hormone in the index stimulation cycle of IVF treatment in predicting outcome of subsequent frozen-thawed embryo transfers

This retrospective cohort study aims at determining whether baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the index stimulation cycle predict live-birth outcome in subsequent frozen-thawed embryo transfer (FET) cycles. We studied 500 women undergoing the first IVF cycle who had embryo(s) cryopreserved. The main outcome measures were live-birth in the first FET cycle and cumulative live-birth in all the FETs combined after the same stimulation cycle. Our results showed that baseline AFC and AMH level on the day before ovarian stimulation showed significant correlation. In the first FET cycle, AFC and AMH level were significantly higher in subjects attaining live-birth in the first FET cycle or cumulative live-birth from all FETs than those who did not. Both AMH and AFC were insignificant predictors of live-birth in the first FET cycle or cumulative live-birth after adjusting for age. The areas under the ROC curves for AMH, AFC and age were 0.654, 0.625 and 0.628, respectively, for predicting cumulative live-birth. In conclusion, we reported for the first time that baseline AFC and AMH in the index stimulation cycle have only modest predictive performance on cumulative live-birth in subsequent FET cycles.

Influence of somatic cell donor breed on reproductive performance and comparison of prenatal growth in cloned canines

Using in vivo–flushed oocytes from a homogenous dog population and subsequent embryo transfer after nuclear transfer, we studied the effects of donor cells collected from 10 different breeds on cloning efficiency and perinatal development of resulted cloned puppies. The breeds were categorized into four groups according to their body weight: small (≤9 kg), medium (>9–20 kg), large (>20–40 kg), and ultra large (>40 kg). A total of 1611 cloned embryos were transferred into 454 surrogate bitches for production of cloned puppies. No statistically significant differences were observed for initial pregnancy rates at Day 30 of embryo transfer for the donor cells originated from different breeds. However, full-term pregnancy rates were 16.5%, 11.0%, 10.0%, and 7.1% for the donor cells originated from ultra-large breed, large, medium, and small breeds, respectively, where pregnancy rate in the ultra-large group was significantly higher compared with the small breeds (P < 0.01). Perinatal mortality until weaning was significantly higher in small breeds (33.3%) compared with medium, large, or ultra-large breeds where no mortality was observed. The mean birth weight of cloned pups significantly increased proportional to breed size. The highest litter size was examined in ultra-large breeds. There was no correlation between the number of embryo transferred and litter size. Taken together, the efficiency of somatic cell cloning and fetal survival after embryo transfer may be affected significantly by selecting the appropriate genotype.

The hysteroscopy and histological diagnosis and treatment value of chronic endometritis in recurrent implantation failure patients

To study the consistency of hysteroscopy findings and histological chronic endometritis (CE) in recurrent implantation failure (RIF) cases, and to compare their values in indicating antibiotic treatment. Sixty RIF cases (January 2009-January 2010) and 202 consecutive RIF cases (May 2010-April 2012) in Peking University Third Hospital reproductive medical center were studied. 60 RIF patients' endometrial samples redid section and CD38/CD138 immunohistochemical stain for CE screening. In 202 RIF cases, the presence of hyperemia, mucosal edema, and micropolyps under hysteroscopy were considered CE diagnostic parameters. Antibiotic was offered to part of the patients. The patients' clinical outcomes were analyzed by statistical methods. In 202 RIF cases, the hysteroscopy CE rate was 66.3 %, while histological CE rate was 43.6 %. The sensitivity and specificity of hysteroscopy were 35.2 and 67.5 %. In histological CE patients, 68 cases underwent regular antibiotic treatment and 20 did not. Two groups had similar clinical pregnancy rates (35.3 vs. 30.0 %), embryo implantation rates (18.9 vs. 20.4 %) and ongoing pregnancy rates (29.4 vs. 25.0 %). In hysteroscopy CE patients, the implantation rate (18.6 vs. 4.9 %) and ongoing pregnancy rate (29.3 vs. 7.4 %) significantly increased (P < 0.05) with antibiotic treatment, and higher intrauterine pregnancy rate in treatment group (29.3 vs. 11.1 %). In reviewing the chosen 60 RIF cases, the histological CE rates were similar in both pregnancy and non-pregnancy group after subsequent embryo transfer. CE occurs frequently in RIF patients; hysteroscopy has more diagnostic and treatment value for them.

Role of Ultrasound in the Assessment of Female Infertility

ABSTRACT Ultrasound has made significant advancements in reproductive medicine, especially infertility of a female cause. It is a useful tool in the diagnosis and management of various disorders. Transvaginal ultrasonography in particular plays a vital role in infertility treatment as it allows for evaluation of normal and stimulated ovarian cycles, aspiration of follicles, and subsequent transfer of embryos. The use of color Doppler permits visualization of endometrial and intraovarian vessels, facilitating an understanding of normal and abnormal physiology of the uterus and ovaries. This article reviews a variety of case scenarios regarding female infertility that may be encountered in the practice of reproductive endocrinology. Ovarian causes such as polycystic ovarian syndrome, luteinized unruptured follicle, luteal phase defect, premature ovarian failure, and endometriosis, are discussed together with tubal and uterine causes of infertility. By using illustrative images, the reader will be able to correlate findings on B-mode, color Doppler and 3D ultrasound with various causes of female infertility. How to cite this article Sheikh M, Kupesic Plavsic S. Role of Ultrasound in the Assessment of Female Infertility. Donald School J Ultrasound Obstet Gynecol 2014;8(2):184-200.

Reducing multiple births in assisted reproduction technology

Multiple pregnancy, a complication of assisted reproduction technology, is associated with poorer maternal and perinatal outcomes. The primary reason behind this is the strategy of replacing more than one embryo during an assisted reproduction technology cycle to maximise pregnancy rates. The solution to this problem is to reduce the number of embryos transferred during in-vitro fertilisation. The transition from triple- to double-embryo transfer, which decreased the risk of triplets without compromising pregnancy rates, was easily implemented. The adoption of a single embryo transfer policy has been slow because of concerns about impaired pregnancy rates in a fresh assisted reproduction technology cycle. Widespread availability of effective cryopreservation programmes means that elective single embryo transfer, along with subsequent frozen embryo transfers, could provide a way forward. Any such strategy will need to consider couples' preferences and existing funding policies, both of which have a profound influence on decision making around embryo transfer.

Fresh transfer outcome predicts the success of a subsequent frozen transfer utilizing blastocysts of the same cohort

The objective of this retrospective analysis was to assess whether the outcomes of fresh blastocyst transfer cycles are predictive of the chances for pregnancy and live birth in subsequent frozen blastocyst transfer cycles using sibling embryos from the same retrieval. Clinical pregnancy rate (CPR) and live birth rate (LBR) per fresh and frozen blastocyst transfer were assessed. All subgroups had similar patient and cycle characteristics. Overall, CPR and LBR in fresh cycles were 44% and 29%, and in frozen were 34% and 30%, respectively. However, the CPR and LBR in frozen cycles were significantly higher in patients who were not pregnant with their fresh cycles (CPR 43% versus 22%, P=0.01; and LBR 36% versus 17%, P=0.03, respectively). When fresh cycles are unsuccessful, the remaining frozen blastocysts of the same cohort have the same chance of success in producing a clinical pregnancy as the fresh cycle (43% versus 44%). Frozen cycles following successful fresh cycles have significantly lower CPR and LBR. These data reinforce the concept that only a few embryos per cohort are competent for a live birth.During IVF cycles, many patients are fortunate enough to have excess high-quality embryos remaining after their embryo transfer. These embryos can be frozen, or cryopreserved, for later transfer. The transfer of cryopreserved embryos increases the cumulative success rates after a single IVF stimulation. Many studies have examined success rates such as clinical pregnancy rate and live birth rate in frozen embryo transfer cycles. While these frozen embryo transfer cycles have excellent success rates, they are significantly lower than success rates in cycles where a “fresh”, non-frozen, embryo is transferred. Few studies have carefully examined the impact of the result of the fresh embryo transfer (whether the patient became pregnant or not) on subsequent frozen embryo transfer success. Here we show that women who are not pregnant after a fresh embryo transfer have higher success rates in subsequent frozen embryo transfer cycles that use frozen embryos generated during a single IVF cycle. In these women (not pregnant after a fresh embryo transfer), frozen embryo transfer pregnancy rates are the same as rates using fresh embryos.

Treatment of chronic endometritis in women with implantation failure improves implantation in subsequent embryo transfers

Controversy exists regarding whether chronic endometritis (CE) negatively impacts embryonic implantation. Our aim was to determine if CE and subsequent antibiotic treatment positively impacts implantation in women undergoing IVF-embryo transfer (ET) who had previously failed to conceive despite transfer of high quality embryos.

Frozen thawed oocytes and embryos for trophectoderm biopsy (TE)

To determine if previously vitirfied oocytes and embryos can be thawed and oocytes fertilized and then be subjected to TE biopsy and either re-vitrified for a subsequent frozen embryo transfer (FET) cycle, or held in culture overnight for a “rush” PGD with embryo transfer (ET).

Transfer of warmed euploid blastocysts significantly improves live birth rates for infertility patients of advanced maternal age (>35 YEARS): A randomized control trial

Advanced maternal age (AMA) is a primary cause of human infertility and is the most significant risk factor for embryo chromosome aneuploidy that characteristically results in failed implantation or miscarriage. The objective of this study was to evaluate a method that could improve live birth rates for infertile AMA women involving blastocyst comprehensive chromosome screening (CCS) with a subsequent frozen embryo transfer (FET).

Follicle recruitment determines IVF productivity rate via the number of embryos frozen and subsequent transfers

IVF productivity rate is an index defined as the sum of all live births from either fresh or frozen embryo transfers arising from a single oocyte collection. This retrospective analysis over 9 continuous years used this index to understand the potential impact on pregnancy rates of milder stimulation regimens with associated reduced egg numbers. The productivity rate per collection increased in a linear and significant rate as more oocytes were recovered, more embryos frozen and more frozen embryo transfers contributed to pregnancy. This observation was true for women aged <35years and less so for women aged 35–39years but not for women aged 40years and older. The contribution of frozen embryo transfer to the productivity rate rose in a linear manner, reaching over 40% of all live births with nine oocytes. The number of live births per oocyte, pronuclear embryos and thawed embryos decreased significantly but the number of live births per embryo transferred (fresh or frozen) rose with rising oocyte numbers, reflecting increasing opportunity for embryo selection. This study suggests that optimal benefits with minimal risks are gained from a model that includes both fresh and frozen transfers under stimulation generating between 8 and 12 eggs.Most of the costs and risks associated with an IVF cycle occur during the stimulation, egg collection and subsequent transfer of fresh embryos and ignore or treat separately the outcome from any subsequent frozen embryo transfers. We have used the term ‘productivity rate’ (or cumulative pregnancy rate per collection cycle) that includes outcomes from both fresh and frozen transfers as a tool to explore the impact of oocyte numbers on the ultimate chance of pregnancy. While the pregnancy rate for individual fresh and frozen transfers were largely unrelated to oocyte numbers, the cumulative chance of pregnancy rose significantly with the number of oocytes recovered. This was due to the increasing contribution of frozen embryo transfers to the overall chance of pregnancy producing more than half of all pregnancies above five oocytes. While the fertilization rate and embryo quality was independent of egg numbers, increasingly more embryos needed to be used to generate sufficient good-quality embryos for transfers as the egg numbers rose. The study found that 8–12 oocytes provided the highest cumulative chance of pregnancy with the least risk of either failed fertilization or ovarian hyperstimulation syndrome and this range could be used as a target number for individualized stimulation regimens.

Update in polycystic ovary syndrome: new criteria of diagnosis and treatment in Japan.

Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women of reproductive age. In 2006 the Japanese Society of Obstetrics and Gynecology (JSOG) proposed new, revised diagnostic criteria that in the future could also be valued internationally. Based on the new diagnostic criteria, the JSOG has also proposed the revised treatment criteria in 2008. In PCOS obese patients desiring children, weight loss and exercise is recommended. Nonobese patients, or those obese women who do not ovulate after lifestyle changes, are submitted to ovulation‐induction therapy with clomiphene citrate (CC). Obese CC‐resistant patients who have impaired glucose tolerance or insulin resistance are treated with a combination of metformin and CC. If these treatments options are unsuccessful, ovulation induction with exogenous gonadotropin therapy or laparoscopic ovarian drilling (LOD) is recommended. A low‐dose step‐up regimen is recommended with careful monitoring in order to reduce the risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. Alternatively, with LOD high successful pregnancy rates of around 60 % are expected with a low risk of multiple pregnancies. If ovulation induction is unsuccessful, IVF‐ET treatment is indicated. In high OHSS‐risk patients, systematic embryo freezing and subsequent frozen embryo transfer cycles are recommended. In nonobese, anovulatory PCOS patients not desiring children, pharmacological treatments such as Holmström, Kaufmann regimens or low‐dose oral anticonceptives are used to induce regular withdrawal bleeding. These treatments are especially important for preventing endometrial hyperplasia and endometrial cancer. These new diagnostic and treatment criteria hopefully will contribute to an improved care of PCOS patients in Japan.

Dynamics of intracellular phospholipid membrane organization during oocyte maturation and successful vitrification of immature oocytes retrieved by ovum pick-up in cattle

The objective was to determine if immature bovine oocytes with cumulus cells at the germinal vesicle (GV) stage could be vitrified by aluminum sheets (AS; pieces of sheet-like aluminum foil). Cleavage rates in fertilized oocytes previously vitrified by the AS procedure were higher than those vitrified by a nylon-mesh holder (NM) procedure (89.3 ± 2.1% vs. 65.0 ± 3.7%). Cleaved embryos derived from the AS but not from the NM procedures developed to blastocysts. Furthermore, to investigate the effects of vitrifying GV oocytes on cytoplasmic structure and on the ability to undergo cytoplasmic changes, the intracellular phospholipid membrane (IM) was stained with the lipophilic fluorescent dye, 3,3′-dioctadecyloxa-carbocyanine perchlorate. After vitrification by AS, the IM remained intact relative to that of oocytes vitrified by NM. During in vitro maturation, reorganization of the IM was also undamaged in oocytes vitrified by AS before oocyte maturation, and the IM within oocytes vitrified by the NM procedure was evidently impaired. Finally, vitrification (AS) was used for GV oocytes collected using the ovum pick-up method. A bull calf was born after in vitro production and subsequent embryo transfer. The vitrification techniques described herein should facilitate generation of viable in vitro production bovine blastocysts using oocytes recovered using the ovum pick-up method.

Clomiphene Citrate as An Adjuvant to hMG Stimulation of the Ovaries in Mid-to-late Follicular Phase and Subsequently Pregnancy Outcome of Frozen-thawed Embryo Transfers

To compare the results of a novel regimen of human menopausal gonadotrophin (hMG) in combination with clomiphene citrate (CC) in mid-to-late follicular phase with those of a short protocol of GnRH agonist (GnRHa) and hMG used for IVF. In the retrospective study, 842 patients undergoing IVF were collected and classified into two groups: hMG in combination with CC in mid-to-late follicular phase (group A, n=319) and short protocol of GnRHa-hMG (group B, n=523). The main outcome measures were ovarian responses in stimulation cycles and pregnancy outcomes in subsequent frozen-thawed embryo transfer (FET) cycles. In group A, the serum LH concentration on day 8–10 was similar with that on the day of hCG administration (2.43± 1.92 IU vs 2.51 ± 2.05 IU). The number of mature follicles and oocytes retrieved was significantly lower in group A than in group B while the fertilization rate and the cleavage rate were comparable. The clinical pregnancy rate (47.79% vs 48.04%), the implantation rate (32.49% vs 33.11%) and the cumulative pregnancy rate (58.09% vs 60.22%) were respectively similar in group A and group B. hMG in combination with CC in mid-to-late follicular phase results in the same pregnancy outcome as short protocol. The novel protocol may take the advantage of eliminating the occurrence of a premature endogenous LH surge.