Luteal estrogen supplementation in stimulated cycles may improve the pregnancy rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer.

OBJECTIVE: To evaluate the effect of estradiol addition to progesterone supplementation during the luteal phase on pregnancy and implantation rates in patients undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. METHODS: In this prospective, randomized study, carried out in an IVF unit of a university hospital, we studied patients who were undergoing IVF/ICSI with controlled ovarian hyperstimulation using a gonadotropin-releasing hormone agonist/human recombinant gonadotropin long protocol. The main outcome measures were the pregnancy and implantation rates measured in the two groups. RESULTS: Our results suggest higher pregnancy and implantation rates in IVF/ICSI-ET cycles that were supplemented with estradiol in the luteal phase. CONCLUSIONS: Estradiol supplementation during the luteal phase in women undergoing IVF/ICSI-ET has a beneficial effect on the outcome without (at least, as seems from this study) having any adverse effects.     

Conservative Management versus Aspiration of Functional Ovarian Cysts Before Ovarian Stimulation for Assisted Reproduction

Purpose: To compare the efficiency of transvaginal ultrasound-guided functional ovarian cyst aspiration, withconservative management, in the outcome of patientsundergoing assisted reproductive technique (ART) (in vitrofertilization or intracytoplasmic sperm injection). Thesecysts were identified before ovarian stimulation begun andafter administration of a midluteal GnRH agonist. Methods: Fifty nine patients undergoing ART from January1, 1997 to February 28, 1999, who developed functionalovarian cysts were included. Aspirations of these cysts(n = 14) versus conservative management(n = 45) were compared. Total number of ovarian folliclesdeveloped, number of oocytes retrieved, estradiol levels onthe day of human chorionic gonadotropin, fertilization rate,number of good quality embryos transferred, implantation,and clinical pregnancy rate per cycle were evaluated. Results: No statistical differences were observed betweenthe two groups in any of the selected parameters. Conclusions: Cyst aspiration and conservative managementshowed similar implantation and pregnancy rates, in patientswho develop functional ovarian cysts after pituitarydown-regulation following luteal phase gonadotropin-releasinghormone agonist administration. Prospective studies areneeded to confirm this trend.     

Luteal estrogen supplementation in stimulated cycles may improve the pregnancy rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection–embryo transfer

Objective. To evaluate the effect of estradiol addition to progesterone supplementation during the luteal phase on pregnancy and implantation rates in patients undergoing in vitro fertilization/intracytoplasmic sperm injection–embryo transfer (IVF/ICSI-ET) cycles.

Methods. In this prospective, randomized study, carried out in an IVF unit of a university hospital, we studied patients who were undergoing IVF/ICSI with controlled ovarian hyperstimulation using a gonadotropin-releasing hormone agonist/human recombinant gonadotropin long protocol. The main outcome measures were the pregnancy and implantation rates measured in the two groups.

Results. Our results suggest higher pregnancy and implantation rates in IVF/ICSI-ET cycles that were supplemented with estradiol in the luteal phase.

Conclusions. Estradiol supplementation during the luteal phase in women undergoing IVF/ICSI-ET has a beneficial effect on the outcome without (at least, as seems from this study) having any adverse effects.     

Comparison between two forms of vaginally administered progesterone for luteal phase support in assisted reproduction cycles

The use of progesterone for luteal phase support has been demonstrated to be beneficial in assisted reproduction cycles using gonadotrophin-releasing hormone analogues (GnRHa). Two micronized progesterone preparations are available for vaginal administration: capsules and gel. The objective of this study was to compare the efficacy of these two forms for luteal phase support in assisted reproduction cycles. A total of 244 couples undergoing IVF/intracytoplasmic sperm injection cycles were included in the study and were randomly allocated (sealed envelopes) into two groups: group 1 (122) received vaginal capsules of 200 mg of micronized progesterone (Utrogestan), 3 times daily, and group 2 (122) received micronized progesterone in gel (Crinone 8%), once daily. Both groups received progesterone for 13 days beginning day 1 after oocyte retrieval, continuing until the pregnancy test was performed and until 12 weeks of pregnancy. Groups were compared by clinical data and assisted reproduction results and had similar ages and causes of infertility. Although the pregnancy rate was higher for those receiving progesterone gel than capsules (44.26 and 36.06% respectively), this difference was not statistically significant. The study showed that vaginal progesterone gel and capsules used for luteal phase support in assisted reproduction cycles with long protocol GnRHa result in similar pregnancy rates.     

Effect of duration of the GnRH agonists in the luteal phase in the outcome of assisted reproduction cycles

Abstract

The effect of long-acting GnRHa, in the luteal phase, during ART cycles varies from one patient to another. The aim of this study was to evaluate whether the effect of long-acting GnRHa in the luteal phase, in ART cycles, affects pregnancy rates according to the duration of its action in such phase. This is a retrospective study of 367 patients submitted to ovulation induction for in vitro fertilization/intracytoplasmic sperm injection procedures that used long-acting depot GnRHa for pituitary suppression. Patients were stratified according to the period of action of the agonist in the luteal phase: group 1, ≤6 days; group 2, 7 to 12 days; and group 3, >12 days. The following variables were analyzed: ovarian response, age, infertility causes and pregnancy rates. Group 1 (n?=?53) had a mean age of 33.8?±?4.55 years (23–44 years) and a pregnancy rate of 45.2%. In group 2 (n?=?118), mean age was 33.7?±?4.5 years (24–44 years) and the pregnancy rate was 38.9%. In group 3 (n?=?196), mean age was 33.7?±?4.4 years (23–43 years) and the pregnancy rate was 47.4%. Regardless of the duration of depot GnRHa action in the luteal phase, no significant association with pregnancy rates was found.     

A randomized prospective study comparing supplementation of the luteal phase and early pregnancy by natural progesterone administered by intramuscular or vaginal route]

Deficiency in the luteal phase has been shown during stimulated cycles using a protocol involving a GnRH agonist. The authors undertook a randomised prospective trial of supplementation by progesterone of the luteal phase and of early pregnancy in two hundred and seventy two patients requiring fertilisation in vitro (FIV), gamete inter-fallopian transfer (GIFT) or zygote inter-fallopian transfer (ZIFT). Either progesterone in solution in oil (50 mg/day) administered by intramuscular injection or micronized progesterone administered intra-vaginally (600 mg/d) were used as support for the luteal phase. Administration of progesterone in association with estradiol valerate was started on the day prior to oocyte puncture and was continued until the 12th week of pregnancy. The implantation rate was very close to the threshold of significance (P = 0.07) in favour of the patients given vaginal progesterone. There was a higher rate of clinical pregnancies (33.6 versus 26.7 p. cent) in the latter group, though this was not significant. While plasma progesterone (Pg) levels were lower in patients using vaginal progesterone, the abortion rate during the first three months was lower in this group (P < 0.05). Micronized progesterone administered vaginally was well tolerated by all patients. During stimulated cycles, notably by GnRHa, it thus proved to be more effective than Pg administered by intramuscular injection with regard to implantation and abortion rates.     

An alternate approach to controlled ovarian hyperstimulation in "poor responders": pretreatment with a gonadotropin-releasing hormone analog

Pharmacologic hypophysectomy was induced with a subcutaneous injection of leuprolide acetate before the administration of exogenous gonadotropins for multiple follicle development in 27 women who had previously responded poorly to conventional controlled ovarian hyperstimulation (COH). Pituitary desensitization occurred within 6 days and concurrent COH with exogenous gonadotropins resulted in an enhanced yield of oocytes in comparison to previous COH attempts (P less than 0.05). Fertilization and pregnancy rates also were higher with gonadotropin-releasing hormone agonist (GnRHa) treatment (P less than 0.01). The administration of leuprolide acetate effectively suppressed endogenous gonadotropin secretion when initiated in the follicular or luteal phase of the menstrual cycle. GnRHa therapy can appreciably facilitate the management of gonadotropin therapy, and increase the probability of oocyte collection and pregnancy.     

The effect of intramural and subserous uterine fibroids on implantation and clinical pregnancy rates in patients having intracytoplasmic sperm injection

Our objective was to assess the effects of intramural and subserous fibroids on intracytoplasmic sperm injection (ICSI) in a retrospective case-control study of 108 women with uterine fibroids and 324 controls. The fibroids were located and measured by transvaginal ultrasound performed just before the ICSI cycle and all patients had normal endometrial scan. Seventy-three women had intramural and 35 women had subserous fibroids and the maximum diameter in any patient ranged from 0.5–10 cm. The number of fibroids in a patient ranged from 1–8. The first cycle outcome was compared with an age and body mass index matched 324 ICSI patients/cycles. All couples had male factor infertility. The ICSI cycles of patients with intramural and subserous fibroids were comparable in terms of the days of ovarian stimulation, the total dose of gonadotropin used, estradiol level on day of hCG administration, the number of metaphase II oocytes retrieved, fertilization and cleavage rates, number and quality of embryos developed and transferred. The implantation and clinical pregnancy rates were similar. We conclude that the presence of intramural and subserous fibroids does not adversely effect clinical pregnancy and implantation rates in patients undergoing ICSI. Received: 3 January 2001 / Accepted: 16 March 2001     

Embryo transfer and luteal support in natural cycles

Embryo transfer policy and luteal supplementation was reviewed, comparing literature data and the results from the Maribor IVF Centre. A retrospective analysis of 1024 cycles in patients undergoing IVF, intracytoplasmic sperm injection (ICSI) or testicular sperm aspiration in unstimulated cycles was carried out using four different approaches for cycle monitoring. This showed that the most successful protocol for monitoring was administration of human chorionic gonadotrophin (HCG) when serum oestradiol was >0.49 nmol/l and follicle diameter was at least 15 mm. The implantation rate per transferred embryo was higher when a blastocyst was transferred (42.8%) rather than a day-2 embryo (23.5%) in the same monitoring protocol. Analysis of the influence of patient age on the success of oocyte retrieval, oocyte fertilization, embryo transfer rate and delivery rate demonstrates that patient age does not influence the rate of positive oocyte retrieval or fertilization rate as much as it influences pregnancy rate per embryo transfer. The delivery rate per cycle was dramatically influenced by age in patients over 38 years. There is no clear evidence in the literature as to whether luteal phase support is necessary in natural cycles for IVF/ICSI. Comparing the data, a higher pregnancy rate was observed if HCG was administered after embryo transfer.     

The gonadotropin-releasing hormone antagonist protocol--the protocol of choice for the polycystic ovary syndrome patient undergoing controlled ovarian stimulation

Polycystic ovary syndrome (PCOS) patients are prone to develop ovarian hyperstimulation syndrome (OHSS), a condition which can be minimized or completely eliminated by the use of a gonadotropin-releasing hormone agonist (GnRHa) trigger. In this commentary paper, we maintain that the gonadotropin-releasing hormone antagonist protocol should be the protocol of choice for the PCOS patient undergoing ovarian stimulation with gonadotropins for in vitro fertilization. If an excessive ovarian response is encountered, the clinician will always have two options: either to trigger final oocyte maturation with a bolus of GnRHa and supplement the luteal phase with a small bolus of human chorionic gonadotropin in addition to the standard luteal phase support and transfer in the fresh cycle or, alternatively, to trigger with GnRHa and perform a total freeze, resulting in a complete elimination of OHSS and high ongoing pregnancy rates in the subsequent frozen-thawed transfer cycles.     

Value of suppression with a gonadotropin-releasing hormone agonist prior to gonadotropin stimulation for in vitro fertilization

This study examined the use of gonadotropin-releasing hormone agonist (GnRHa) suppression before gonadotropin stimulation in 26 patients with failed prior in vitro fertilization (IVF) attempts and variable basal serum gonadotropin levels. Leuprolide, 1 mg subcutaneously per day, was administered from the midluteal phase of the cycle before IVF treatment. Concomitantly, stimulation was initiated on cycle day 3 with human menopausal gonadotropin (hMG) and follicle stimulating hormone (FSH). Based on their prior IVF attempts and serum gonadotropin levels on cycle day 3, 9 patients were high responders with elevated mean basal luteinizing hormone (LH)/FSH, 8 were low responders with elevated mean basal FSH/LH, 7 were intermediate responders with normal mean basal FSH/LH and a history of premature LH surge, and 2 had elevated (perimenopausal) mean FSH and LH. Leuprolide was discontinued on the day of human chorionic gonadotropin (hCG) administration. Prior IVF attempts in the same patients with the same protocol, but without GnRHa suppression, were used as controls. The mean number of ampules of hMG and FSH was significantly higher in leuprolide cycles than in controls. The mean day of hCG administration was also higher for leuprolide cycles than for controls. The mean LH and progesterone levels on the day of hCG were significantly lower in leuprolide cycles. The mean number of preovulatory oocytes aspirated and transferred was higher in leuprolide cycles. Cancellation and pregnancy rates were improved in leuprolide cycles. It is concluded that prior GnRHa suppression is beneficial for follicular recruitment for IVF. More patients with variable basal serum gonadotropin levels need to be studied before definite recommendations are made.     

A comparison of 3-day and daily follicle-stimulating hormone injections on stimulation days 1-6 in women undergoing controlled ovarian hyperstimulation

OBJECTIVE: To evaluate the efficacy of ovarian hyperstimulation by intermittent doses of 450 IU of recombinant human (h)FSH compared with daily 150-IU doses of recombinant hFSH. DESIGN: A pilot, open, randomized, parallel-group study. SETTING: Center for Reproductive Medicine, Düsseldorf, Germany. PATIENT(S): Infertile women with indication for IVF/intracytoplasmic sperm injection after at least 1 year of unprotected intercourse. INTERVENTION(S): Recombinant hFSH was administered daily or intermittently (3-day intervals) from days 1 to 6 of stimulation and thereafter by daily injection. MAIN OUTCOME MEASURE(S): Number of preovulatory follicles, retrieved oocytes, two-pronuclei (2PN) zygotes, implantation, and pregnancy rates. RESULT(S): The number of oocytes in the daily-dose group was significantly greater. There were no significant differences in mean values for number of follicles > or =11 mm (except for day 7) and > or =14 mm, 2PN zygotes, and number of transferred embryos. Implantation and pregnancy rates per cycle were in favor of the intermittent 450-IU dose regimen; implantation rates were 17.0% and 9.8% in the 3-day-dose and daily-dose groups, respectively, and biochemical and clinical pregnancy rates were 33.3% and 15.7% and 25.5% and 13.7%, respectively. CONCLUSION(S): Intermittent administration of recombinant hFSH significantly reduces the total number of recombinant hFSH injections, compared with a conventional FSH regimen, without detrimental effects on implantation rate or pregnancy rate.     

Additive hormonelle Therapie bei der assistierten Reproduktion

The article summarizes the knowledge in March 2014 regarding estradiol, progesterone and gonadotropin-releasing hormone (GnRH) agonist administration during the luteal phase after assisted reproductive technologies (ART). The administration of estradiol does not influence the therapeutic outcome. Progesterone supplementation leads to a significantly increased live birth rate after gonadotropin stimulation. Prolonged treatment with progesterone beyond the positive human chorionic gonadotropin (hCG) test has no further beneficial effects on live birth and miscarriage rates. The single administration of a low dose GnRH agonist 5 or 6 days after follicular puncture does not increase the ongoing pregnancy rate in stimulated in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) agonist and antagonist cycles.     

Intracytoplasmic sperm injection versus in vitro fertilization for patients with a tubal factor as their sole cause of infertility: a prospective, randomized trial

OBJECTIVE: To compare the efficacy of intracytoplasmic sperm injection and IVF in women with a tuboperitoneal factor as their sole cause of infertility. DESIGN: Prospective, randomized study. SETTING: Hacettepe University Assisted Reproduction Unit, Ankara, Turkey. PATIENT(S): Seventy-six consecutively seen patients with tuboperitoneal factor infertility were randomized on an alternate basis to undergo either intracytoplasmic sperm injection (38 patients and cycles) or IVF (38 patients and cycles). INTERVENTION(S): Intracytoplasmic sperm injection and IVF. MAIN OUTCOME MEASURE(S): Fertilization, implantation, and clinical pregnancy rates. RESULT(S): A comparable number of oocytes and embryos were obtained with intracytoplasmic sperm injection and IVF. The two-pronuclei fertilization rates per metaphase II oocyte or mature cumulus-oocyte complex were similar in the two groups. The numbers of total and grade I embryos transferred also were similar. Comparisons of intracytoplasmic sperm injection and IVF did not reveal any statistically significant differences in individual implantation rates (38.75% +/- 24.46% and 34.58% +/- 16.97%, respectively) clinical pregnancy rates per cycle (21.05% and 21.05%, respectively), or take-home infant rates (18.42% and 15.79%, respectively). The type of procedure performed was not a significant predictor of clinical pregnancy. CONCLUSION(S): When a decision is made to proceed with an assisted reproductive technique in patients with a tubal factor as their sole cause of infertility, IVF should be the initial treatment of choice.     

Administration of a GnRH agonist during the luteal phase frozen–thawed embryo transfer cycles: a meta-analysis

Abstract

At present, the precise role of GnRH agonists during the luteal phase remains uncertain. In the present study, a meta-analysis was used to evaluate the effect of administering a GnRH agonist to during the luteal phase in patients undergoing FET cycles. A literature review was carried out by searching the current content of MEDLINE, Embase, the Cochrane Controlled Trials Register and Ovid. We particularly focused upon implantation rate, CPR per transfer, and ongoing pregnancy rate. All of the trials analyzed involved a GnRH agonist administered during the luteal phase. Six trials involving 1137 women were included in our meta-analysis. All of the cycles analyzed exhibited significantly higher implantation rates, clinical pregnancy rates, and ongoing pregnancy rates in the group of patients administered with a GnRH agonist during the luteal phase compared with the control group that did not receive a GnRH agonist during the luteal phase. Our data, therefore, demonstrate that the administration of a GnRH agonist during the luteal phase can significantly increase clinical pregnancy and ongoing pregnancy rates in FET cycles. The implantation rates, clinical pregnancy rates, and ongoing pregnancy rates can significantly increase in the group of patients administered with a GnRH agonist in natural cycle FET.     

Does addition of low-dose aspirin and/or steroid as a standard treatment in nonselected intracytoplasmic sperm injection cycles improve in vitro fertilization success? A randomized,prospective, placebo-controlled study

Purpose: To investigate the effects of short-term low-dose aspirin and/or steroid use on implantation and pregnancy rates in nonselected intracytoplasmic sperm injection (ICSI) cycles. Methods: Two-hundred patients undergoing ICSI for their first cycle were enrolled in this study. Participants were then randomized into four groups on the embryo transfer day. Aspirin (100 mg/day) in group A, prednisolone (10 mg/day) in group B, aspirin along with prednisolone in group C were given while placebo was administrated to group D. Result: There were no statistically significant differences recorded in the demographic, ovulation induction cycle characteristics between groups. Mean transferred embryo number and mean top quality embryo number were similar among study groups. There were no statistical differences in implantation and pregnancy rates between study groups. Conclusion: Administration of low-dose aspirin and prednisolone alone or concomitant as a standard treatment have no positive effects on implantation and/or pregnancy rates.     

The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives

In stimulated IVF/intracytoplasmic sperm injection cycles, the luteal phase is disrupted, necessitating luteal-phase supplementation. The most plausible reason behind this is the ovarian multifollicular development obtained after ovarian stimulation, resulting in supraphysiological steroid concentrations and consecutive inhibition of LH secretion by the pituitary via negative feedback at the level of the hypothalamic-pituitary axis. With the introduction of the gonadotrophin-releasing hormone-(GnRH) antagonist, an alternative to human chorionic gonadotrophin triggering of final oocyte maturation is the use of GnRH agonist (GnRHa) which reduces or even prevents ovarian hyperstimulation syndrome (OHSS). Interestingly, the current regimens of luteal support after HCG triggering are not sufficient to secure the early implanting embryo after GnRHa triggering. This review discusses the luteal-phase insufficiency seen after GnRHa triggering and the various trials that have been performed to assess the most optimal luteal support in relation to GnRHa triggering. Although more research is needed, GnRHa triggering is now an alternative to HCG triggering, combining a significant reduction in OHSS with high ongoing pregnancy rates.     

Does the timing of mock embryo transfer trial improve implantation in intracytoplasmic sperm injection cycles?

Aim.?To determine if endometrial trauma during embryo transfer trials (ETTs) improves implantation and clinical pregnancy rates in intracytoplasmic sperm injection treatment cycles.

Patients.?One-hundred fifty women undergoing their first IVF treatment were included in a prospective randomised study in a University hospital clinic. ETTs were performed either on day 21 of the previous cycle, or on day 6 of the controlled ovarian hyperstimulatin (COH) cycle, or conducted at least two cycles before COH cycle. Clinical pregnancy and implantation rates were compared between the groups.

Results.?There was no difference between the groups in terms of clinical pregnancy or implantation rates.

Conclusion.?Endometrial trauma by ETTs performed either during the preceeding cycle or on day 6 of the COH cycle does not improve pregnancy rates.     

Luteal start of exogenous FSH in poor responder women

Purpose To compare the effectiveness of using recFSH commenced in the luteal phase with a long GnRH agonist protocol or in the early follicular phase with a short GnRH agonist protocol, in infertile women designated as poor responders undergoing treatment with assisted reproduction in a prospective, randomized, controlled study. Materials and methods Forty-two couples undergoing an ICSI cycle of whom female partner diagnosed as poor responder were included in the study. Recombinant FSH was given daily from day 21 of the previous cycle upon initiation of GnRH agonist in the study group. Control group was given FSH on day 2 in a short protocol GnRH agonist regimen. The number of metaphase 2 oocytes was analysed as the main outcome measure; pregnancy rate and clinical pregnancy rate were secondary outcome measures. Results Patients in the study group had significantly higher number of metaphase 2 oocytes. Although not statistically significantly patients in the study group had higher pregnancy/clinical pregnancy rates, as well. Conclusion This preliminary study shows that luteal start of recFSH simultaneously with long protocol GnRH agonist in poor responder women produced better results comparing to short protocol GnRH agonist plus high dose FSH regimen. Capsule: Luteal administration of recFSH along with GnRHa in poor responder women in an ART cycle increases metaphase 2 oocyte number significantly comparing to GnRHa flare-up protocol     

Low-Dose Aspirin Does Not Increase Implantation Rates in Patients Undergoing Intracytoplasmic Sperm Injection: A Prospective Randomized Study

Purpose: The aim was to evaluate the effect of aspirin on pregnancy and implantation rates in an unselected group of patients undergoing intracytoplasmic sperm injection (ICSI). Methods: Two hundred and seventy-nine patients were randomized to receive 80 mg of aspirin (n = 139) or no treatment (r = 136) starting from the first day of controlled ovarian hyperstimulation. Results: Duration of stimulation, gonadotropin consumption, peak estradiol, number of oocytes retrieved, fertilization rate, cleavage rate, and number of embryos transferred were similar in the two groups. Implantation and clinical pregnancy rates were 15.6% and 39.6% versus 15.1% and 43.4% in aspirin treated and untreated groups, respectively (P > 0.05). Conclusions: Low-dose aspirin administration does not improve implantation and pregnancy rates in an unselected group of patients undergoing ICSI.