Endocrinology: Progesterone alone versus progesterone combined with HCG as luteal support in GnRHa/HMG induced IVF cycles: a randomized clinical trial

Two different regimens of luteal support in gonadotrophin hormone-releasinghormone (GnRH) analoguefhuman menopausal gonadotrophin (GnRHa/HMG)-inducedin-vitro fertilization cycles (IVF) were compared in a randomizedclinical trial. After embryo transfer, either vaginal progesteronealone was administered (n=89, P group), or a combination ofvaginal progesterone and human chorionic gonadotrophin (n=87,P/HCG group). The primary aim of this study was to assess theeffect of the different regimens of luteal support on the pregnancyrate. The secondary aim was to compare oestradiol and progesteroneconcentrations in the luteal phase between the two groups, andassess their effect on the pregnancy rate. A clinical pregnancyrate of 15% was found in the P/HCG group in comparison with26% in the P group (odds ratio 0.49; 99% confidence interval:0.18–1.3). The luteal serum oestradiol and progesteronevalues in the P/HCG group were significantly higher when comparedwith the P group on the 6th, 9th and 12th day after oocyte retrieval(Wilcoxon P<0.001). In accordance with the high oestradiolconcentrations, more cases of ovarian hyperstimulation syndrome(OHSS) were found in the P/HCG group. Oestradiol values on the9th day after oocyte retrieval, presumably the day of implantation,appeared to be higher in women who did not become clinicallypregnant. We conclude that vaginal progesterone alone providessufficient luteal support in GnRHa/HMG induced IVF cycles. Thecombination of vaginal progesterone and HCG as luteal supportleads to significant high luteal oestradiol and progesteroneconcentrations. But a high concentration of oestradiol seemsto have a deleterious effect on the implantation process, resultingin a low pregnancy rate.     

Does ICSI affect early serum beta-HCG in pregnancies achieved after IVF?

This study was conducted to compare early serum human chorionic gonadotrophin (HCG) concentrations in singleton pregnancies achieved after intracytoplasmic sperm injection (ICSI), with those achieved after conventional in-vitro fertilization (IVF). Early serum HCG, 14-16 days after embryo transfer, was analysed in 99 IVF pregnancies achieved after ICSI (group A), and compared to 105 conventional IVF pregnancies (group B). All women were treated at the IVF Unit, Lis Maternity Hospital. Records were studied retrospectively. The mean +/- SE serum HCG concentration on day 14 after embryo transfer in group A was 190.5 +/- 17.4 mIU/ml, compared to 195.7 +/- 14.03 mIU/ml in group B. HCG concentration 14 days after embryo transfer in both groups A and B was higher in women with mechanical factor than in couples with male factor infertility or unexplained infertility (246 +/- 31.4, 183.3 +/- 16.4, 177.98 +/- 14.3 mIU/ml respectively). On the 16th day after embryo transfer, the HCG concentration increased, and the difference between the groups was maintained. Only in the subgroup of unexplained infertility did we find a difference in concentrations of HCG between ICSI and conventional IVF: on the 16th day following embryo transfer in this group there was a significant difference in HCG concentrations (395. 8 +/- 21 and 545.6 +/- 45.7 respectively; P = 0.04). HCG concentrations did not differ overall in the conventional IVF pregnancies compared with those achieved by ICSI. However, a statistical difference in early serum HCG concentrations was found in relation to the aetiology of infertility.     

In-vitro fertilization and the ovarian hyperstimulation syndrome.

Eight patients who developed severe ovarian hyperstimulation syndrome (OHSS) were identified among 1302 patients undergoing in-vitro fertilization (IVF) over a 1 year period (prevalence of 0.6%); 63% had ultrasonically diagnosed polycystic ovaries (PCO) and 75% were undergoing their first attempt at IVF. Pretreatment with a superactive luteinizing hormone-releasing hormone (LHRH) analogue significantly increased the prevalence of severe OHSS (1.1% versus 0.2%, P less than 0.05) compared with ovarian stimulation with clomiphene citrate and human menopausal gonadotrophin (HMG). The mean serum oestradiol concentration on the day of human chorionic gonadotrophin (HCG) administration was 8200 +/- 2300 pmol/l. A mean of 19.6 +/- 6.8 follicles had been aspirated and 13.1 +/- 7.7 oocytes recovered at transvaginal ultrasound-directed oocyte recovery. All patients had an embryo transfer and luteal support in the form of HCG. The clinical pregnancy rate was 88%, multiple pregnancy rate 71% and implantation rate 63.5 +/- 41.3%. In a group of seven patients who were hospitalized for moderate OHSS during the same period, peak oestradiol levels were significantly lower than in those with severe OHSS (P less than 0.05). Of the group with moderate OHSS, 57% had PCO, the clinical pregnancy rate was 100% and multiple pregnancy rate 43%. Patients with ultrasound-diagnosed PCO have an increased risk of developing OHSS and the dose of HMG administered to them should be minimized. In patients at risk of developing OHSS, progesterone instead of HCG should be used for luteal support. Transfer of a maximum of two embryos or freezing all embryos for transfer in a subsequent cycle may reduce the likelihood of multiple pregnancy.     

Ratio of oestradiol concentration on the day of human chorionic gonadotrophin administration to mid-luteal oestradiol concentration is predictive of in-vitro fertilization outcome.

The role of luteal oestradiol for successful implantation in humans seems to be permissive rather than obligatory. Few studies have attempted to clarify the role of early luteal oestradiol in in-vitro fertilization (IVF) outcome, whether peri-implantation oestradiol is predictive of successful IVF outcome. We retrospectively analysed 106 women undergoing 106 IVF/embryo transfer cycles. Only the first treatment cycle per patient was analysed. Peak oestradiol denoted the concentration on the day of human chorionic gonadotrophin (HCG) administration. Mid-luteal oestradiol was obtained 3 days after embryo transfer (8 days after HCG administration). A total of 44 pregnancies were noted (41.51%). There were no differences in age, cycle day 3 follicle stimulating hormone (FSH), peak oestradiol, number of retrieved oocytes, number of embryo transfers, and mid-luteal oestradiol between pregnant and non-pregnant women. However, the ratio of day of HCG oestradiol to mid-luteal oestradiol was highly predictive of successful outcome: the ongoing pregnancy rate and implantation rate (sacs with fetal heart beat/embryo transfer) were 15.8 and 5.7% respectively if the above ratio exceeded 5.0 (n = 19), compared to 42.1 and 16.3%, and 53.3 and 26. 5% if the ratio was between 0.4 and 2.5 (n = 57), and between 2.5 and 5.0 (n = 30) respectively. Our study suggests that the magnitude of decline in oestradiol concentrations after oocyte retrieval may be important in predicting IVF success. We postulate that endometrial integrity may become compromised when a dramatic drop in oestradiol occurs by the mid-luteal period. Whether these women benefit from oestradiol supplementation after oocyte retrieval remains to be investigated.     

The effect of luteal support with human chorionic gonadotrophin or progesterone on the daily progesterone profile after different types of ovarian stimulation.

Attempts have been made to increase the low pregnancy rate in in-vitro fertilization (IVF) cycles by luteal phase support with progesterone or human chorionic gonadotrophin (HCG). Previously, this practice has been inconsistent and the results unclear. The detailed effect of support on the progesterone profile in the luteal phase was assessed by daily salivary progesterone measurements in non-conception IVF cycles. The comparison of HCG and progesterone support in two different stimulation protocols showed that the profile of luteal progesterone concentrations was similar in control cycles and those supported with a vaginal progesterone suppository, showing an early decrease by the fourth luteal day. In cycles supported with multiple doses of HCG, the progesterone profile was normal but slightly increased up to the 9th luteal day subsequently falling to basal levels by the fourteenth luteal day.     

Serum progesterone at the time of human chorionic gonadotrophin does not predict pregnancy in in-vitro fertilization and embryo transfer

Controversy exists as to whether the serum concentration ofprogesterone on the day of human chorionic gonadotrophin (HCG)administration following ovarian stimulation for in-vitro fertilization(IVF) and embryo transfer can be used to predict the likelihoodof success. This retrospective study was undertaken to answerthis question by analysing a large population of IVF and embryotransfer cycles (n = 756). In addition to the concentrationof progesterone on the day of HCG administration, all variablesknown to impact on IVF and embryo transfer success (such aspatient age), indication for IVF and embryo transfer, numberof oocytes retrieved and the number of embryos generated andtransferred were examined. There was a significant increasein the number of oocytes retrieved with increasing progesteroneconcentration at the time of HCG administration. However, therewas no correlation of progesterone concentration at HCG administrationwith pregnancy and implantation rates. It is concluded thatprevious reports associating a slight elevation of progesteronein gonadotrophin- releasing hormone agonist ovarian stimulationcycles for IVF and embryo transfer may be misleading becauseof a small sample size or the presence of confounding variablesthat affect IVF and embryo transfer success.     

Timing luteal phase support in GnRH agonist down-regulated IVF/embryo transfer cycles

BACKGROUND: The aim of this study was to compare the effect of three different times of onset of luteal phase support on ongoing pregnancy rate in infertile patients undergoing treatment with GnRH down-regulated IVF and embryo transfer (IVF/ET). MATERIALS AND METHODS: All consecutive eligible patients planned to undergo their first IVF treatment cycle were randomly allocated to receive vaginal progesterone as luteal support at three different time points, that is, after HCG administration for final oocyte maturation (HCG group), at the day of oocyte retrieval (OR group) or at the day of ET (ET group). The primary endpoint of this study was ongoing pregnancy rate. RESULTS: A total of 385 women were randomized, 130 were allocated to the HCG group, 128 to the OR group and 127 to the ET group. An ongoing pregnancy rate of 20.8% was found in the HCG group versus 22.7 and 23.6% in the OR group and ET group, respectively. The mean number and quality of the retrieved oocytes and the transferred embryos did not differ. CONCLUSION: Based on this data, an 18% difference in ongoing pregnancy rate between the three different times of onset of luteal phase support in GnRH agonist down-regulated IVF/ET cycles can be refuted. Smaller clinically meaningful differences may be present.     

Elevated serum progesterone on the day of HCG administration in IVF is associated with a higher pregnancy rate in polycystic ovary syndrome

Our study compared 84 patients with polycystic ovary syndrome (PCOS) with 84 control patients who had normal ovaries and who were matched for the main determinants of success in in-vitro fertilization (IVF) and embryo transfer. Serum concentrations of oestradiol and progesterone on the day of human chorionic gonadotrophin (HCG) injection were significantly higher in PCOS than in normal patients (oestradiol 2016 +/- 1.8 pg/ml versus 1456 +/- 40.9 pg/ml, P < 0.01; progesterone 1.6 +/- 0.1 ng/ml versus 1.2 +/- 0.1 ng/ml, P = 0.03). Furthermore despite oocytes from PCOS patients having a reduced fertilization rate compared with normal patients (61.8 +/- 4.1% versus 73.5 +/- 4.3%, P = 0.03), the differences in pregnancy rate (22.6 versus 19%) and miscarriage (31.5 versus 18.7%) were not statistically significant. In PCOS patients, a critical breakpoint was identified at serum progesterone concentrations of 1.2 ng/ml on the day of HCG injection. The PCOS patients with progesterone > or = 1.2 ng/ml showed a higher pregnancy and miscarriage rate than PCOS patients with progesterone < 1.2 ng/ml (26.6 versus 17.9%, P < 0.01; and 41.7% versus 14.3%, P < 0.01 respectively). These findings suggest that premature progesterone production does not have an adverse effect on pregnancy rate in PCOS, but on the contrary, may be a predictor for success in IVF/embryo transfer.     

Progesterone supplementation during early gestations after IVF or ICSI has no effect on the delivery rates: a randomized controlled trial

BACKGROUND: The aim was to study whether prolongation of luteal support during early pregnancy influences the delivery rate after IVF. METHODS: Dual centre study including 303 women who achieved pregnancy after IVF or ICSI was used. All were treated with the long protocol using GnRH agonists and given luteal support with 200 mg vaginal progesterone three times daily during 14 days from the day of transfer until the day of a positive HCG test. The study group (n = 150) withdrew vaginal progesterone from the day of positive HCG. The control group (n = 153) continued administration of vaginal progesterone during the next 3 weeks of pregnancy. RESULTS: The number of miscarriages prior to and after week 7 of gestation was seven (4.6%) and 15 (10.0%) in the study group and five (3.3%) and 13 (8.5%) in the control group respectively. The number of deliveries was 118 (78.7 %) in the study group and 126 (82.4 %) in the control group. The differences were not significant. CONCLUSIONS: Prolongation of progesterone supplementation in early pregnancy has no influence on the miscarriage rate, and thus no effect on the delivery rate. Progesterone supplementation can safely be withdrawn at the time of a positive HCG test.     

Hormonal influence on the uterine contractility during ovarian stimulation

High-frequency uterine contractions (UC) at the time of embryo transfer have been shown to hamper the outcome of in-vitro fertilization (IVF). As UC are postulated to be hormone-regulated, we aimed to investigate the role of plasma oestradiol and progesterone concentrations on UC during ovarian stimulation for IVF. A total of 59 women were studied on the day of administration of human chorionic gonadotrophin (HCG) and embryo transfer. Plasma oestradiol and progesterone concentrations were measured, and 5 min ultrasound scans of the uterus were digitized with an image analysis system to assess UC frequency and direction. Cycles were sorted according to whether progesterone concentrations on the day of embryo transfer were < or =100 (n = 34) or >100 (n = 25) ng/ml. On the day of HCG, UC frequency was similar in both groups at 4.5+/-0.2 and 4.6+/-0.3 UC/min (mean +/- SE) respectively. On the day of embryo transfer, UC frequency remained steady in the low progesterone group, whereas it decreased (3.5+/-0.2 UC/min) in the high progesterone group (P < 0.001), and was negatively correlated with progesterone concentrations (r = -0.56; P < 0.001). No influence of oestradiol on UC was noticed. These observations confirm the utero-relaxing effects of progesterone in the non-pregnant uterus and support the administration of progesterone before embryo transfer to increase tissue concentrations and improve the outcome of IVF.     

A prospective randomized trial of human chorionic gonadotrophin or dydrogesterone support following in-vitro fertilization and embryo transfer

A randomized, prospective blind study was carried out to investigate the need for luteal phase support in patients undergoing in-vitro fertilization (IVF). One-hundred-and-fifty-six patients undergoing IVF in cycles stimulated with human menopausal gonadotropin (HMG) and human chorionic gonadotrophin (HCG) stimulated IVF, were divided into three different groups for luteal phase treatment. Fifty-four patients received dydrogesterone three times daily (TID) beginning on the day of embryo transfer (ET). Fifty-one patients received HCG on days 3, 6 and 10 following ET. Fifty-one patients received placebo p.o. TID beginning on the day of ET. There was no difference between the groups in pregnancy rate, rate of spontaneous abortion, proportion of normally developing fetuses or rate of chemical pregnancy. The data indicate that supplementation of the luteal phase may not improve the success rates of IVF-ET cycles.     

Sonographic appearance of the endometrium: the predictive value for the outcome of in-vitro fertilization in stimulated cycles.

We evaluated the predictive value for pregnancy of the endometrial thickness and pattern assessed by vaginal sonography on the day of human chorionic gonadotrophin (HCG) injection and the day of embryo transfer in 74 stimulated cycles for in-vitro fertilization (IVF) which were analysed prospectively. Thickness was measured from the echogenic interface of the endometrial-myometrium junction in transverse fundal sections. The distribution of endometrial pattern on the day of HCG was 19 A (poor quality) cases (25.7%) and 55 B (good quality) cases (74.3%). On the day of embryo transfer, 16 out of the 19 A cases (84%) remained as A pattern, while the remaining three cases (16%) had changed to B pattern; of the 55 B cases, 29 (53%) remained the same, while 26 cases (47%) changed to A pattern. There was no significant correlation between the endometrial pattern on the day of HCG and/or on the day of embryo transfer and the peak serum oestradiol levels, the number of preovulatory oocytes aspirated, the serum progesterone levels and oestradiol: progesterone ratio on the day of transfer. In contrast, on the day of HCG, endometrial thickness correlated with serum oestradiol levels on that day (P = 0.02). The presence of pattern A on the day of HCG was associated with a lower pregnancy rate [three out of 19 cases, (15.8%)], compared to pattern B [16 out of 55 cases, (29.1%)], although this was not statistically significant (P greater than 0.05). On the day of embryo transfer, comparable pregnancy rates between A pattern [11 out of 42 cases, (26.1%)] and B pattern [eight out of 32 cases, (25%)] were found.(ABSTRACT TRUNCATED AT 250 WORDS)     

Colour Doppler indices of follicular blood flow as predictors of pregnancy after in-vitro fertilization and embryo transfer.

Peak systolic velocity (PSV) of individual follicles has been correlated with oocyte recovery, fertilization rate and embryo quality [in women undergoing in-vitro fertilization (IVF) and embryo transfer]. The present study assessed the role of quantitative and qualitative indices of follicular vascularity in predicting pregnancy after IVF and embryo transfer. A total of 106 women undergoing IVF treatment for infertility who were considered to be at risk of failure (>37 years of age, history of low response to gonadotrophin stimulation, or multiple failed IVF cycles) constituted the study group. PSV was measured from the three largest follicles on both the right and left ovaries on the day of human chorionic gonadotrophin (HCG) administration using an Acuson Sequoia with a 4-8 MHz transvaginal probe. The quality of follicular flow was graded from 1 to 4 according to the amount of visible colour flow around the follicle (grade 1 when one-quarter of the follicle, grade 2 when one-half, grade 3 when three-quarters, and grade 4 when the entire follicle was surrounded by colour). Clinical pregnancies resulted in 11 (10%) of the 106 high-risk women. Women who had PSV >/= 10 cm/s in at least one follicle on the day of HCG administration more often became pregnant than those with PSV <10 cm/s (P = 0.05). All pregnancies occurred in women with grade 3 or 4 follicular blood flow. Qualitative as well as quantitative measurements of follicular flow predict pregnancy after IVF and embryo transfer.     

Luteal phase support in in-vitro fertilization using gonadotrophin releasing hormone analogue before ovarian stimulation: a prospective randomized study of human chorionic gonadotrophin versus intramuscular progesterone.

This study was conducted to compare the endocrine milieu and pregnancy rates in an in-vitro fertilization and embryo transfer (IVF-ET) programme employing a gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) when either human chorionic gonadotrophin (HCG) or progesterone were used for luteal phase support. A total of 121 IVF-ET treatment cycles were prospectively studied. All patients started leuprolide acetate in the midluteal phase and it was continued for at least 10 days. When oestradiol levels were less than 150 pmol/l, HMG was started. When at least three follicles were greater than or equal to 17 mm in diameter, HCG 5000 IU i.m. was given. Oocytes were retrieved using transvaginal ultrasound and embryos were transferred 48 h later. The patients' cycles were prospectively randomized to receive HCG (72 cycles) or progesterone (49 cycles) luteal support. The HCG group received 1500 IU i.m. on days 3, 6 and 9 after the initial trigger. The progesterone group received 12.5 mg i.m. q.d. starting from the day after the HCG trigger. The dose of progesterone was increased to 25 mg i.m. q.d. starting on the day of embryo transfer and continued for 17-21 days. If the patient became pregnant, this dose of progesterone was continued until fetal heart activity was visualized by ultrasound. Mean ages, number of eggs retrieved, embryos transferred, oestradiol levels on the day of the HCG trigger, oestradiol and progesterone at the time of embryo transfer were the same in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human chorionic gonadotrophin concentrations in early pregnancy after in-vitro fertilization.

There is increased risk of early pregnancy loss after assisted reproduction. In this study the use of serum human chorionic gonadotrophin (HCG) concentrations on day 12 after in-vitro fertilization (IVF) and embryo transfer was evaluated to predict pregnancy outcome. A total of 417 IVF pregnancies were included. Early pregnancy loss was defined as biochemical pregnancies, ectopic pregnancies and first trimester abortions. Vital pregnancies were defined as delivered singletons, multiple pregnancies and second trimester abortions. On the post embryo transfer day 12, the mean HCG concentration of the vital pregnancy group was significantly higher than in early pregnancy loss outcomes (P < 0.00001). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the cut-off value of HCG giving maximal sensitivity and specificity in order to discriminate early pregnancy losses from vital pregnancies. A patient with a HCG value higher than the calculated cut-off value (55 IU/l) had a 90% chance of having a vital pregnancy after IVF and embryo transfer. It can be concluded that a discriminatory HCG value on day 12 after IVF and embryo transfer cycles may be useful in predicting pregnancy outcome and may guide clinicians in identifying those pregnancies at risk for adverse outcomes and instituting more intensive surveillance in this population.     

Uterine contractility decreases at the time of blastocyst transfers

High-frequency uterine contractions at the time of non-cavitating embryo transfer influence adversely IVF-embryo transfer outcome. This prompted us to quantify prospectively the possible decline in uterine contraction frequency occurring during later stages of the luteal phase of ovarian stimulation, up to the time of blastocyst transfers, in 43 IVF-embryo transfer candidates. Contractility was assessed on the day of human chorionic gonadotrophin (HCG) administration, 4 days after HCG (non-cavitating embryo transfer; HCG + 4), and 7 days after HCG (blastocyst transfers; HCG + 7). For this, 2 min sagittal uterine scans were obtained by ultrasound and digitized with a computerized system for the assessment of uterine contraction frequency. Our results indicated that a slight, yet significant, decrease in uterine contraction frequency, observed from the day of HCG (4.4 +/- 0.2 contractions/min) to HCG + 4 (3.5 + 0.2 contractions/min), was followed by a more pronounced, additional decrease between HCG + 4 and HCG + 7 (1.5 +/- 0.2 contractions/min; P < 0.001). In conclusion, during the luteal phase of ovarian stimulation, uterine contractility decreases progressively, and reaches a nearly quiescent status 7 days after HCG administration, at the time of blastocyst transfers. It is possible that such a uterine relaxation assists blastocyst implantation.     

Sex hormone-binding globulin, oestradiol-17 beta, progesterone and testosterone at stimulation and after embryo transfer during in-vitro fertilization.

Serum concentrations of sex hormone-binding globulin (SHBG), oestradiol-17 beta progesterone and testosterone were measured in 23 gonadotrophin-stimulated menstrual cycles and in the implantation period [days 11-19 after human chorionic gonadotrophin (HCG) injection] following in-vitro fertilization and embryo transfer. Nine cycles resulted in successful pregnancies, one pregnancy ended in spontaneous abortion (week 14) and 13 cycles were without conception. SHBG levels were significantly elevated above pretreatment values from day 3 after HCG injection onwards. A significant positive correlation was found between increments in SHBG (delta SHBG) during the luteal phase and oestradiol/testosterone ratios during the follicular and luteal phases. In the pregnant cycles a significant positive correlation was also found between delta SHBG during the implantation period and oestradiol/testosterone ratios during the luteal phase and the implantation period. Significant negative correlations were found between delta SHBG and testosterone during the luteal phase in pregnant and non-pregnant women as well as between delta SHBG during the period corresponding to implantation and testosterone during the luteal phase in non-pregnant cycles. The results may reflect a modulating action of the oestrogen/androgen balance upon SHBG levels in subjects with supraphysiological oestradiol levels, such as in stimulated cycles and in very early pregnancy.     

黄体中期E2变化对IVF-ET结局的影响

目的研究黄体中期（ET后第3日）E2变化对IVF—ET结局的影响。方法放免法检测270例首次行IVF—ET助孕患者注射HCG日和黄体中期的外周血E2水平，根据黄体中期E2变化分为增高组（Group Ⅰ）和降低组（GroupⅡ），GroupⅡ又根据E2降低百分比进一步分为A、B、C、D四组，比较各组的种植率和临床妊娠率。结果GroupⅠ和GroupⅡ之间以及A、B、C、D各组间的种植率和临床妊娠率均无显著统计学差异（P〉0．05）。临床妊娠组和未妊娠组在HCG日和黄体中期E2水平、黄体中期E2升高比率和降低比率方面均无显著统计学差异（P〉0．05）。结论单纯评价黄体中期E2水平变化不能预测IVF—ET结局。     

Hormonal and histological evaluation of the luteal phase after combined GnRH-agonist/gonadotrophin treatment for superovulation and luteal phase support in in-vitro fertilization.

A hormonal and histological study of the luteal phase was performed in 21 stimulated in-vitro fertilization (IVF) patients not undergoing embryo transfer. Ovarian stimulation was carried out with gonadotrophins [follicle stimulating hormone (FSH) + human menopausal gonadotrophin (HMG)] under pituitary suppression with buserelin. Ovulation was induced with 5000 IU human chorionic gonadotrophin (HCG) and additional doses of 5000, 2500 and 2500 IU were given on the day of follicular aspiration, and 2 and 5 days later respectively, to support the luteal phase. Supraphysiological levels of oestradiol (E2) and progesterone in plasma were found in the midluteal phase of all women, while prolactin was in the normal range. An endometrial biopsy taken in the late luteal phase was normal in 90.5% (19/21) of patients, most of them (15/19, 79%) having E2 greater than 1500 pg/ml on the day of HCG. Conversely, both patients with defective endometrial biopsies had E2 levels less than 1500 pg/ml.     

Luteal support with micronized progesterone following in-vitro fertilization using a down-regulation protocol with gonadotrophin-releasing hormone agonist: a comparative study between vaginal and oral administration.

This study aimed to compare the efficacy of micronized progesterone administered as luteal support following ovulation induction for in-vitro fertilization (IVF)- embryo transfer in cycles using gonadotrophin-releasing hormone agonist, either orally (200 mgx4/day) or vaginally (100 mgx2/day) and to characterize the luteal phase hormonal profile during such treatments. A total of 64 high responder patients requiring intracytoplasmic sperm injection due to male factor infertility were prospectively randomized into two treatment groups. Patients treated orally or vaginally were comparable in age (31.9 +/- 6.1 versus 30.6 +/- 5.2; mean +/- SD), number of oocytes retrieved (17 +/- 8.2 versus 18 +/- 7.0), and number of embryos transferred (3.1 +/- 1.2 versus 2.7 +/- 0.9) per cycle. Following low dose vaginal treatment, a significantly higher implantation rate (30.7 versus 10.7%, P < 0.01), but similar clinical pregnancy rate (47.0 versus 33.3%) and ongoing pregnancy rate (41.1 versus 20.0%) was observed, compared with oral treatment. In conception cycles, luteal serum progesterone and oestrogen concentrations did not differ between the treatment groups. In non-conception cycles, late luteal progesterone concentrations were significantly lower following vaginal treatment. As low dose micronized progesterone administered vaginally is simple, easy and well tolerated, it could be recommended as the method of choice for luteal support, especially for high responder patients at risk for ovarian hyperstimulation syndrome.