The luteal phase after in-vitro fertilization and related procedures

To evaluate any beneficial effect of progesterone supplemen–tationduring the luteal phase of GIFT or IVF cycles stimulated byclomiphene citrate and HMG, two random prospective studies wereperformed. In the first study, a group of patients receiveda luteal phase supplement of 50 mg natural progesterone i.m.daily from the day of oocyte retrieval onwards. Initial resultson 168 patients indicated that the pregnancy rate was similarin patients with or without progesterone supplements. No differenceswere found between the two groups in an analysis of pregnantand failed cycles. In a second study two different protocolsof luteal phase sup–plementation after Buserelin–HMGstimulation were com–pared: natural progesterone in combinationwith oestradiol valerate (50 patients) or HCG supplements (41patients). A 32% pregnancy rate per cycle was encountered inboth groups. Endometrial biopsies, taken during the luteal phasefrom patients who did not undergo embryo replacement, revealedretarded endometrial development in most of the biopsies.     

Evaluation of the luteal phase

The values of various methods used to evaluate the luteal phase, including basal body temperature, measurement of progesterone (P), endometrial biopsy, ultrasonographic measurement of endometrial thickness, and measurement of endometrial proteins, are reviewed. Luteal phase defect (LPD) is a controversial entity. The diagnosis of this condition is best based on a histological study of the endometrium. Methods to improve the accuracy of the diagnosis are discussed. LPD is more likely to be a result of an abnormal response of the endometrium to P, than to a subnormal production of P by the corpus luteum. Many methods of treatment for LPD have been proposed but none is based on a properly controlled clinical trial. Treatment designed to improve the response of the endometrium to P may be more rewarding than P supplementation.     

Efficacy of progesterone support in the luteal phase following in-vitro fertilization and embryo transfer: meta-analysis of clinical trials

The question of whether follicular aspiration of oocytes altersthe quality of the luteal phase remains unanswered. Progesteroneappears to be necessary for implantation and maintenance ofan early intrauterine pregnancy and this partly has been thebasis for recommending luteal phase supplementation with progesteronefollowing oocyte retrieval. Although small increases in pregnancyrates were observed in several trials, such support with progesteronewas not efficacious. However, none of the studies had sufficientstatistical power to detect small improvements in pregnancyrate. Pooling the results of these trails using several methodsof meta-analysis has allowed an overall effect of treatmentto be calculated. This effect, as measured by the odds ratio,was not significant, indicating that there was insufficientevidence to recommend the routine use of progesterone to supportthe luteal phase after oocyte retrieval.     

High fecundity rates in donor oocyte recipients and in-vitro fertilization surrogates using parenteral oestradiol valerate

Ovum donation and in-vitro fertilization (IVF) surrogacy canhelp couples with difficult infertility problems achieve pregnancy.Most centres using oral oestrogens and oestradiol patches reportpregnancy rates in the range of 30% per cycle. Parenteral oestradiolvalerate has pharmacological properties that make it an attractiveoption for preparing the endometrium in the recipients undergoingthese procedures. When the egg providers were under age 35 years,and using oestradiol valerate in the recipients, we achieveda 61% clinical pregnancy rate in 62 cycles. These improved resultssuggest that parenteral oestradiol valerate should be used toprepare the endometrium in recipients, and that the hormonalmilieu of the endometrium plays an important role in the higherimplantation rates obtainable in ovum donor and IVF surrogatecycles.     

Pregnancy: Adverse effect of a homogeneous hyperechogenic endometrial sonographic pattern, despite adequate endometrial thickness on pregnancy rates following in-vitro fertilization

We have previously presented data to show that in patients whohad in-vitro fertilization (IVF)—embryo transfer usingovarian stimulation involving the luteal phase leuprolide acetate—humanmenopausal gonadotrophin (HMG) regimen, poor pregnancy resultsensued if either the endometrial thickness was < 10 mm ora homogeneous hyperechogenic sonograpic pattern was presentimmediately prior to taking a human chorionic gonadotrophin(HCG) injection. There were only 15 cases with this hyperechogenictype endometrium (and no pregnancies). The purpose of the presentstudy was to evaluate the influence of a hyperechogenic endometriumwhen the endometrial thickess was 10 mm, in a more extensiveseries, in women having IVF—embryo transfer using thesame ovarian stimulation regimen. A total of 273 consecutivecycles, where endometrial thickness was 10 mm, were evaluated(not including the 85 cycles previously reported). Of 22 patientswith the hyperechogenic pattern, one achieved a chemical pregnancy(-HCG >500 mIU/ml) and none achieved clinical pregnancies(ultrasound confirmation). In contrast, 67 of 251 (26.7%) patientsconceived with other echo patterns (x² analysis = 5.9, df =1, P = 0.01). These data thus confirm, in a larger series, thenegative influence of this type of echo pattern on subsequentpregnancy rates following the luteal phase leuprolide acetate—HMGovarian stimulation regimen.     

The usefulness of endometrial biopsy for luteal phase evaluation in infertility.

To assess the usefulness of the late luteal phase endometrial biopsy in infertility, we evaluated a total of 1492 biopsies performed in 1055 patients. Of these women, 699 underwent one biopsy during spontaneous ovulatory cycles, 288 had two, 57 had three, nine had four, and five biopsies were done in two patients. As controls we included 45 fertile women who were requesting contraception. We analysed histological dating of the endometrium and its abnormality rates in first and successive biopsy specimens, as well as the association of the pregnancy outcome with the endometrial patterns and treatment for luteal phase deficiency (LPD). Our results show firstly that diagnosis of LPD in both infertile and fertile women represents only a chance event; secondly, histological endometrial adequacy or inadequacy in the cycle of conception or in previous cycles is not related to the outcome of pregnancy in infertile patients. Finally, treatment of LPD does not improve pregnancy outcome in infertile women. Thus, luteal phase evaluation by histological dating of the endometrium is not worthwhile.     

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 relationship between endogenous oestradiol and vitamin D3 metabolites in serum and follicular fluid during ovarian stimulation for in-vitro fertilization and embryo transfer.

The present study was undertaken to examine the effect of circulating oestradiol on serum levels of 25-hydroxyvitamin D3 (25-OHD3), 24,25-dihydroxyvitamin D3[24,25-(OH)2D3], and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] during gonadotrophin-induced ovarian stimulation in 10 healthy women undergoing in-vitro fertilization and embryo transfer (IVF). The presence of these metabolites in the follicular fluid was also investigated. Plasma oestradiol increased from 25 +/- 3.2 (mean +/- SE) pg/ml before initiation of treatment to 2563 +/- 328 pg/ml on the day of injection of human chorionic gonadotrophin (HCG) and 1641 +/- 299 pg/ml on the day of ovum retrieval (P < 0.01). Serum levels of 1,25-(OH)2D3 increased from 32.0 +/- 1.9 (mean +/- SE) pg/ml to 46.6 +/- 8.1 and 48.5 +/- 7.7 pg/ml (P < 0.05) on the day of HCG and ovum retrieval, respectively. No changes in blood levels of 25-OHD3 and 24,25-(OH)2D3 were found. The presence of vitamin D metabolites in follicular fluid is documented herein for the first time. All three metabolites were present in the follicular fluid but were significantly lower than in the concurrent serum (P < 0.01). A highly significant correlation was found between serum and follicular fluid levels: r = 0.787, P < 0.001 for 1,25-(OH)2D3; r = 0.738, P < 0.01 for 25-OHD3; and r = 0.751, P < 0.01 for 24,25-(OH)2D3. Our results suggest that raised levels of circulating oestradiol during gonadotrophin-induced ovarian stimulation are associated with a significant increase of serum 1,25-(OH)2D3.     

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.     

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.     

Results of in-vitro fertilization in normal ovulatory women treated with pure follicle stimulating hormone. Analysis of the oestradiol response

The relationship between various measures of oestradiol (E2) secretion and the total number of oocytes retrieved (OR) and cleaved embryos (CE) was characterized in normal ovulatory women stimulated with pure follicle-stimulating hormone (FSH) in a programme for in-vitro fertilization and embryo transfer (IVF-ET). Patients in this study included women with tubal factor as their only cause for infertility. Cycles were monitored with serum E2 concentration and ultrasonography. Human chorionic gonadotrophin (HCG) was administered when two follicles had a maximum diameter greater than 15 mm. The variables used to characterize the E2 secretory response included: (i) the difference between the highest and lowest E2 concentration during stimulation; (ii) the ratio of terminal to initial E2 concentration; (iii) E2 concentration on the day of HCG administration; and (iv) the slope of the E2 curve. These measures of E2 secretion each correlated with both the number of OR and the number of CE. When all E2 variables were considered simultaneously in a stepwise multivariate regression procedure, variations in the number of OR (r2 = 0.84) or CE (r2 = 0.77) could be explained by variation in the E2 secretory profile. Equations derived from these E2 variables may help to identify and improve problem areas within IVF-ET programmes when actual results differ from expected.     

Correlation of serum progestagen-associated endometrial protein levels with endometrial biopsies serum steroid levels and therapy for luteal phase defects

The progestagen-associated endometrial protein (PEP) level rises from the early to the late luteal phase. A study was performed in infertile women where late luteal phase endometrial biopsies and serum PEP levels were obtained. The objective of the study was to evaluate the correlation between the PEP levels and the endometrial biopsies and to determine if subnormal PEP levels could be improved by the same therapies used to correct endometrial defects. There was a poor correlation between PEP levels and endometrial biopsies (r = 0.17). Similarly, there was no significant correlation between PEP levels and levels of the following hormones: mid- and late-luteal phase progesterone (P) (r = 0.186 and 0.282 respectively), mid-luteal phase 17-hydroxyprogesterone (17-OHP) (r = 0.139) and mid-luteal phase oestradiol (r = 0.135). Furthermore, there was no correlation between PEP levels and the dosage of progesterone used in therapy (r = 0.07). There were no statistically significant differences in PEP values (U/ml) depending on whether any fertility drug was taken. Thus our data suggest that progesterone may only have a permissive role, with some other factor(s) controlling the actual rise and fall of PEP.     

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.     

Ultrasound measurement of endometrial thickness on different ovarian stimulation regimens during in-vitro fertilization

Endometrial thickness was measured ultrasonographically in threegroups of patients undergoing in-vitro fertilization (IVF) onthree different ovulation induction regimens. The endometrialthickness was comparable on all three regimens and similar tothat observed in a group of spontaneously ovulating, normal,fertile controls. These patterns of endometrial thickness wereobserved despite significantly higher levels of serum oestradiol-17In all of the hyperstimulated cycles, suggesting that in thenormal cyde a maximum response in terms of endometrial developmentmay be achieved. In the three conception cycles endometrialthickness continued to increase throughout the luteal phase,whilst In non-conception cycles plateauing of thickness increaseoccurred in the mid-luteal phase and reduction in late lutealphase. Whether ultrasonographic evaluation of endometrium duringIVF stimulation cydes has any prognostic value regarding predictionof conception has yet to be detennined.     

Endocrinology: Daily measurements and in-vitro effects of human chorionic gonadotrophin in the early luteal phase

The purpose of the present study was to analyse daily measurementsof human chorionic gonadotrophin (HCG) in in-vitro fertilization(IVF) cycles and to reproduce the effects of HCG in vitro usinghuman granulosa—luteinized cells from the same patients.The study population consisted of nine women undergoing IVFbecause of tubal infertility in whom blood was drawn every 24h from the day of the ovulatory dose of HCG (10 000 IU) until6 days after ovum pick-up. Granulosa—luteal cells fromthe follicular aspirates were collected and cultured in vitroup to 6 days in the presence of increasing concentrations (0,0.01, 0.1, 1.0 and 100.0 IU/ml) of HCG. Serum progesterone andHCG in vivo as well as progesterone accumulation in vitro ondays 2, 4 and 6, were the main outcome measures. Maximum HCGconcentrations (0.25 IU/ml) were reached the day before ovumpick-up, and continuously decreased until day 6 after ovum retrieval.HCG did not stimulate progesterone production in vitro at anydose tested until day 6 after ovum pick-up. Then, 0.01 IU/mlresulted significantly (P < 0.05) stimulatory compared tocontrols, while 1.0 IU/ml was inhibitory (P < 0.05). It isconcluded that HCG supplementation in an IVF cycle is unnecessaryuntil day 6 after ovum pick-up. On day 6, progesterone productionis stimulated with very low concentrations of HCG.     

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)     

Endocrinology: Luteal phase oestradiol and progesterone levels are stronger predictors than follicular phase follicle stimulating hormone for the outcome of in-vitro fertilization treatment in women with tubal infertility

Basal follicle stimulating hormone (FSH) in a natural cycle,FSH on cycle days 3 and 10 in a domiphene citrate-stimulatedcycle and oestradiol and progesterone area under the curve (AUC)in the luteal phase of the ciomiphene citrate-stimulated cyclewere evaluated as hormonal predictors for the outcome of FVFtreatment in 53 normally cycling women with tubal infertility.The pregnant women had significantly fewer treatment cycles(P < 0.001) and needed fewer ampoules of gonadotrophins (P< 0.001). They also had more oocyte retrievals (P < 0.001),more oocytes per retrieval (P < 0.01), higher fertilizationrate (P < 0.001) and more replaced pre-embryos per replacement(P < 0.01) as compared with non-pregnant women. Significantdifferences were found in FSH concentrations on cycle days 3(P < 0.05) and 10 (P < 0.001) after domiphene citratestimulation and for oestradiol and progesterone AUC in the lutealphase (P < 0.001) between those women who became pregnantand those who did not become pregnant after IVF treatment Lutealoestradiol and progesterone had considerably stronger predictivevalue for the outcome of IVF treatment as compared to basalFSH and domiphene citrate challenge test.     

Serum relaxin and the major endometrial secretory proteins in in-vitro fertilization and down-regulated hormone-supported and natural cycle frozen embryo transfer

Relaxin has been postulated to be a modulator of the expressionof the endometrial secretory proteins, insulin-like growth factorbinding protein (IGFBP-1) and placental protein 14(PP14). Thisstudy evaluated the expression of relaxin in relation to concentrationsof these secretory proteins along with oestradiol, progesteroneand human chorionic gonadotrophin in groups of pregnant andnon-pregnant patients who underwent differing assisted conceptiontreatments. Serum samples were taken from 88 patients at 8 and12 days after embryo transfer. At 12 days after embryo transfer,relaxin concentrations in the pregnant patients who had undergonein-vitro fertilization (IVF) or natural cycle frozen embryotransfer were significantly higher than those who did not conceivein these groups (mean concentrations 8334 versus 28 and 2608versus 62 pg/ml respectively, P <0.001). However concentrationsin the pregnant patients who had hormone support and transferof frozen embryos were not significantly different from thepatients who did not conceive after the same treatment. Althoughrelaxin expression was associated with corpus luteum activity,it was not related to the number of corpora lutea in IVF patients.A wide range of relaxin concentrations was seen to be compatiblewith a healthy pregnancy. These serum relaxin concentrationswere not found to be directly related to the serum concentrationsof IGFBP-1, PP14 or the other factors assessed in this study.     

Endocrinology: Human chorionic gonadotrophin is a better luteal support than progesterone in ultrashort gonadotrophin-releasing hormone agonist/menotrophin in-vitro fertilization cycles

In an attempt to determine the best luteal support in in-vitrofertilization (IVF) cycles treated with gonadotrophin-releasinghormone agonist (GnRHa) and human menopausal gonadotrophin (HMG)by the ultrashort protocol, 60 patients were prospectively randomizedfor either i.m. progesterone or human chorionic gonadotrophin(HCG) luteal support. The two groups did not differ in the meannumber of oocytes retrieved and embryos replaced, nor in themean age of the patients and the amount of HMG used. HCG maintainedhigher levels of oestradiol and progesterone during the lutealphase. Conception rate was significantly higher in the HCG group.We conclude that HCG is superior to i.m. progesterone as lutealsupport in IVF cycles in which GnRHa is used in the ultrashortprotocol.     

The benefits of mid-luteal addition of human chorionic gonadotrophin in in-vitro fertilization using a down-regulation protocol and luteal support with progesterone

Luteal support is essential in in-vitro fertilization (IVF)when long-acting gonadotrophin-releasing hormone agonist (GnRHa)is used. Because progesterone lacks luteotrophic stimulation,it seems to be the drug of choice in cases with an increasedrisk of ovarian hyperstimulation syndrome (OHSS). The aim ofthis study was to assess the beneficial effect of the mid-lutealaddition of human choriomc gonadotrophin (HCG) in IVF, usinga down-regulation protocol and luteal support with progesterone,in a prospective randomized study. The study included 170 IVFcycles down-regulated with long-acting GnRHa which were supportedwith 50 mg/day progesterone i.m. during the luteal phase. Patientswere evaluated in the mid-luteal period. Those without clinicalsigns of OHSS, oestradiol concentrations <1000 pg/ml andprogesterone concentrations <50 mg/ml were randomly allocatedto either the addition of 2500 IU HCG (HCG+ group) or no HCG(HCG– group). End luteal phase progesterone concentrationsamong non-pregnant patients were used to assess the contributionof exogenous progesterone and to categorize pregnancies accordingto their corpus luteum function. Similar low OHSS (2.7 and 1.8%)and pregnancy (30 and 29%) rates were observed in the HCG+ andHCG– groups respectively. Of the 26 pregnancies in theHCG+ cases, there was only one case with reduced corpus luteumfunction, compared with 12 of the 25 pregnancies among HCG–patients. Cases with reduced corpus luteum function requiredcontinuous progesterone support and presented lower HCG concentrationsand a higher rate of adverse pregnancy outcome. We concludethat mid-luteal HCG addition does not affect pregnancy rate,but in fact helps to preserve corpus luteum function and avoidsthe need for further supplementation during early pregnancy.