Embryos derived from single pronucleus are suitable for preimplantation genetic testing.

OBJECTIVE: To study and compare the preimplantation genetic testing for monogenic disorders (PGT-M) results, and to evaluate the treatment cycle outcomes of embryos derived from a single pronucleus (1PN) vs. two pronuclei (2PN). DESIGN: A retrospective cohort study from January 2018 to December 2022 involving in vitro fertilization (IVF)-PGT-M treatment cycles. SETTING: Single, academically affiliated fertility center. PATIENTS: A total of 244 patients underwent 351 IVF-PGT-M treatment cycles. INTERVENTION: Embryo biopsy with molecular testing for a monogenic disorder. MAIN OUTCOME MEASURES: The molecular diagnosis results and clinical outcomes after the transfer of embryos derived from 1PN and 2PN in IVF-PGT-M treatment cycles. RESULTS: Embryos derived from 1PN have a significantly low developmental potential with a lower rate of embryos that underwent biopsy compared with 2PN-derived embryos; 1PN-derived embryos demonstrated a significantly lower number of blastocysts (24% vs. 37.9%) and top-quality blastocysts (22.3% vs. 48.1%) compared with 2PN-derived embryos. Lower successfully completed and unaffected PGT-M results were achieved in 1PN compared with 2PN-derived embryos (47.1% vs. 65.5% and 18.7% vs. 31.6%, respectively), with significantly higher abnormal molecular results (39.6% vs. 22.7%). The embryo transfer of 24 1PN-derived embryos with no affected genetic disorder resulted in 5 (20.8%) clinical pregnancies and 4 (16.7%) live births (LBs). CONCLUSIONS: Within the limits of fewer embryos derived from 1PN that yielded unaffected embryos suitable for transfer, the clinical pregnancy and LB rate of 1PN embryos undergoing PGT-M are reassuring. We, therefore, suggest applying PGT-M to embryos derived from 1PN embryos to improve the cumulative clinical pregnancy and LB rates.

Embryos derived from delayed mature oocyte should be cryopreserved and are favourable to transfer in a following endometrium synchronize frozen-thawed cycle.

Oocytes eligible for intracytoplasmic sperm injection (ICSI) are those that have progressed through meiosis to metaphase 2 (MII). The remaining delayed mature oocytes can be injected, aiming to achieve more embryos and a better chance to conceive. We aimed to assess the outcome of delayed matured oocytes, derived from either germinal vesicles or metaphase 1 (MI), that reached maturity (MII) 24 h following retrieval. The study population consisted of 362 women who underwent 476 IVF cycles. While fertilization rates were comparable between the sibling delayed mature oocyte group compared with injection on day 0 group (58.4% vs 62%, respectively, P = 0.07), the top-quality embryo rate per injected MII day 0 oocyte was significantly higher compared with day 1 injected oocyte (57.5% vs 43.9% respectively, P < 0.001). Moreover, following fresh transfer of embryos derived from delayed mature oocytes, implantation rate and the clinical pregnancy (CPR) and live-birth rates (LBR) per transfer were 3.9%, 3.3% and 1.6% respectively. When considering the following thawed embryo transfer cycles, implantation, pregnancy and LBR were non-significantly higher (10%, 8.3% and 8.3%, respectively). Although clinical outcomes are significantly lower when using embryos derived from delayed mature oocyte to mature day 0 oocytes, the additional embryos derived from delayed mature oocytes might contribute to the embryo cohort and increase the cumulative live-birth rate per retrieval. Moreover, the embryos derived from delayed mature oocyte favour a transfer in a frozen-thawed cycle rather than in a fresh cycle.

GnRH-Agonist Ovulation Trigger in Patients Undergoing Controlled Ovarian Hyperstimulation for IVF with Stop GnRH-Agonist Combined with Multidose GnRH-Antagonist Protocol.

OBJECTIVE: This study aimed to characterize those patients undergoing the stop gonadotropin-releasing hormone (GnRH)-agonist combined with multidose GnRH-antagonist protocol, with suboptimal response to GnRH-agonist trigger in in vitro fertilization (IVF) cycles. DESIGN: This is a cohort study. SETTING: The study was conducted in a university hospital. PATIENTS: All consecutive women admitted to our IVF unit from February 2020 through November 2020 who reached the ovum pick-up stage were reviewed. INTERVENTIONS: Triggering final oocyte maturation by GnRH-ag alone (GnRH-ag trigger group), or combined with hCG (dual trigger group), in patients undergoing the stop GnRH-agonist combined with multidose GnRH-antagonist protocol was performed. MAIN OUTCOME MEASURE: The main outcome measure was LH level 12 h after the trigger. RESULTS: Five out of the 32 patients (15.6%) demonstrated suboptimal response as reflected by LH levels <15 IU/L 12 h after GnRH-agonist trigger. Moreover, while no differences were observed in oocyte recovery rate, maturity, or embryo quality between the different study groups (GnRH-ag trigger and dual trigger groups), those achieving a suboptimal response to the GnRH-agonist trigger (post-trigger LH <15 mIU/mL) demonstrated significantly higher number of follicles and peak estradiol levels at the day of trigger, compared to those with optimal response (post-trigger LH >15 mIU/mL). CONCLUSIONS: The stop GnRH-agonist combined with GnRH-antagonist protocol enables the substitution of hCG with GnRH-ag for final oocyte maturation. However, caution should be taken in high responders, where the dual trigger with small doses of hCG (1,000-1,500 IU) should be considered, aiming to avoid suboptimal response (post-trigger LH levels <15 IU/L).

A Novel Stimulation Protocol for Poor-Responder Patients: Combining the Stop GnRH-ag Protocol with Letrozole Priming and Multiple-Dose GnRH-ant: A Proof of Concept.

OBJECTIVE: The objective of this study was to examine whether the combined Stop GnRH-agonist (GnRH-ag), letrozole priming, and multiple-dose GnRH-antagonist (GnRH-ant) protocol may improve in vitro fertilization/intracytoplasmic sperm injection cycle in poor ovarian responders (PORs). DESIGN: This was a historical cohort, proof of concept study under tertiary setting at University affiliated Medical Center. PATIENTS: Five PORs fulfilling the POSEIDON Group 4 criteria were included. MAIN OUTCOME MEASURES: Number of oocytes retrieved, number of top-quality embryos (TQEs), and controlled ovarian hyperstimulation (COH) variables were the main outcome measures. RESULTS: The combined Stop GnRH-ag, letrozole priming, and multiple-dose GnRH-ant COH protocol revealed significantly higher number of follicles >13 mm on the day of hCG administration and higher number of oocytes retrieved, with non-significantly more TQEs and a reasonable clinical pregnancy rate. CONCLUSIONS: The combined Stop GnRH-ag, letrozole priming, and multiple-dose GnRH-ant COH protocol is a valuable tool in the armamentarium for treating POSEIDON Group 4 patients. Further large prospective studies are needed to elucidate its role in POR and to identify the specific characteristics of women (before initiating ovarian stimulation) that will aid both fertility specialists' counseling and their patients in adjusting the appropriate COH protocol.

The Effect of Ovarian Stimulation on Endothelial Function-A Prospective Cohort Study using Peripheral Artery Tonometry.

CONTEXT: Gonadotropin-releasing hormone agonist (GnRH-a) serves as an alternative to human chorionic gonadotropin (hCG) to trigger final oocyte maturation, while it significantly reduces the risk of ovarian hyperstimulation syndrome (OHSS), probably by attenuating vascular/endothelial activation. OBJECTIVES: The objectives of this work are to compare the effect of different modes of final follicular maturation (hCG vs GnRH-a) following ovarian stimulation (OS) for in vitro fertilization (IVF) on endothelial function. DESIGN AND SETTING: A prospective cohort study was conducted at a tertiary medical center. PARTICIPANTS: Patients age 37 years or younger, undergoing OS for IVF, were allocated into 2 groups according to the type of final follicle maturation: the hCG group (n = 7) or the GnRH-a group (n = 8). INTERVENTION: Endothelial function was assessed by measurement of the peripheral arterial tonometry in reaction to temporary ischemia at 3 study points: day 3 of menstrual cycle (day 0), day of hCG/GnRH-a administration (day trigger) and day of oocyte pick-up (day OPU). The ratio of arterial tonometry readings before and after ischemia is called the reactive hyperemia index (RHI). Decreased RHI (< 1.67) indicates endothelial dysfunction. MAIN OUTCOME MEASURES: The main outcomes measures of this study included endothelial function at 3 study points during OS with different modes of triggering final follicular maturation. RESULTS: The mean RHI values at day 0 were within the normal range for all patients and comparable between both groups (hCG: 1.7 ±â€…0.3 vs GnRH-a: 1.79 ±â€…0.4, P = .6). All patients presented a decrease in RHI values on day trigger, which did not differ between the 2 groups (1.62 ±â€…0.3 vs 1.4 ±â€…0.2, respectively, P = .2). However, the hCG group demonstrated a further decrease in RHI on day OPU, whereas patients who received GnRH-a had restored normal endothelial function reflected by increased RHI values (1.4 ±â€…0.2 vs 1.75 ±â€…0.2, respectively, P = .03). CONCLUSIONS: Triggering final follicular maturation with GnRH-a restored normal endothelial function, whereas hCG trigger resulted in a decrease in endothelial function.

Stop GnRH-Agonist Combined With Multiple-Dose GnRH-Antagonist Protocol for Patients With "Genuine" Poor Response Undergoing Controlled Ovarian Hyperstimulation for IVF.

Objective: To examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may improve conventional IVF/intracytoplasmic sperm injection (ICSI) cycle in poor ovarian response (POR) patients. Design: Cohort historical, proof of concept study. Setting: Tertiary, University affiliated Medical Center. Patient(s): Thirty POR patients, defined according to the Bologna criteria, who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle, were included. For the purposes of this study, we eliminated a bias in this selection by including only "genuine" poor responder patients, defined as those who yielded up to 3 oocytes following COH with a minimal gonadotropin daily dose of 300 IU. Main Outcome Measure(s): Number of oocytes retrieved, number of top-quality embryos, COH variables. Result(s): The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly higher numbers of follicles >13 mm on the day of hCG administration, higher numbers of oocytes retrieved, and top-quality embryos (TQE) with an acceptable clinical pregnancy rate (16.6%). Moreover, as expected, patients undergoing the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol required significantly higher doses and a longer duration of gonadotropins stimulation. Conclusion(s): The combined Stop GnRH-ag/GnRH-ant COH protocol is a valuable tool in the armamentarium for treating "genuine" poor ovarian responders. Further, large prospective studies are needed to elucidate its role in POR and to characterize the appropriate patients subgroup (before initiating ovarian stimulation) that may benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.

Stop GnRH-Agonist Combined with Multiple-Dose GnRH-Antagonist for Patients with Elevated Peak Serum Progesterone Levels Undergoing Ovarian Stimulation for IVF: A Proof of Concept.

AIM: The aim of the study was to examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may overcome progesterone elevation during the late follicular phase. PATIENTS AND METHODS: A cohort historical, proof of concept study consisting of 11 patients with progesterone elevation (>3.1 nmol/L) during conventional IVF/intracytoplasmic sperm injection (ICSI), who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist ovarian stimulation (OS) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle. RESULTS: The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly lower peak progesterone levels, with significantly higher numbers of follicles >13 mm in diameter on the day of hCG administration, oocytes retrieved, mature oocytes, and top-quality embryos, with an acceptable clinical pregnancy rate (18.2%). CONCLUSIONS: The combined Stop GnRH-ag/GnRH-ant OS protocol is a valuable tool in the armamentarium for treating patients with progesterone elevation during the late follicular phase. Further large prospective studies are needed to validate our observation and to characterize the appropriate patients' subgroup, which might benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.

Does double trigger (GnRH-agonist + hCG) improve outcome in poor responders undergoing IVF-ET cycle? A pilot study.

Many strategies are offered for the treatment of poor responders. However, no compelling advantage for one stimulation protocol over another has been hitherto established. In this study, we aimed to evaluate the role of different modes and timings of final follicular maturation trigger, on in vitro fertilization (IVF) cycle outcome of poor responder patients. In the present randomized controlled study, poor responder patients, according to the Bologna criteria, undergoing controlled ovarian hyperstimulation (COH) using the gonadotropin-releasing hormone (GnRH) antagonist protocol were randomly assigned to three different final follicular maturation trigger modes and timings: hCG 36 h before oocyte pick-up (OPU) (hCG trigger); GnRH agonist (GnRHag) 36 h before (OPU) and hCG on day of OPU (GnRHag trigger); and GnRHag and hCG, 40 and 34 h prior to OPU, respectively (double trigger). Pregnancy rate, number of oocytes, and top quality embryos (TQEs). Thirty-three poor responder patients were recruited and randomized to the different study groups. While there were no in-between groups' differences in patients' demographics and stimulation variables, patients in the double trigger group had a significantly higher number of TQE (1.1 ± 0.9 vs. 0.3 ± 0.8 and 0.5 + 0.7; p<.02) as compared to the hCG trigger and the GnRH-ag trigger groups, respectively, with an acceptable pregnancy rate. Double trigger offers an additional benefit to poor responder patients. Larger studies are required to support this new concept prior to its implementation to IVF practice.

GnRH agonist versus GnRH antagonist in ovarian stimulation: the role of elevated peak serum progesterone levels.

AIM: We sought to evaluate the influence of subtle serum progesterone elevation on in vitro fertilization (IVF) cycle outcome and to assess the impact of the type of gonadotropin-releasing hormone (GnRH)-analogue used during controlled ovarian hyperstimulation (COH) on the probability of clinical pregnancy. PATIENTS AND METHODS: We reviewed the files of all consecutive patients undergoing COH with either GnRH-agonist or antagonist in our IVF unit during a 10-year period and who had their peak serum progesterone levels determined on the day of human chorionic gonadotropin (hCG) administration. RESULTS: Of the 2244 IVF cycles evaluated, 2103 had peak progesterone level of <1.5 ng/mL (normal-P group) and 141 of >1.5 ng/mL (high-P group) (6.28% of all the study population). Clinical pregnancy rate was significantly higher in the normal-P group (25.4% versus 16.6%; p < 0.006). Moreover, among the high-P group patients, the use of the long GnRH-agonist suppressive protocol (GnRH-ag) was more prevalent in patients who conceived as compared to those who did not (60.9% versus 39%, respectively; p < 0.05), with a tendency toward an increase pregnancy rate in those using GnRH-ag compared with GnRH-antagonist protocol (GnRH-antag; p < 0.059) COH protocols. CONCLUSION: While subtle progesterone elevation in patients undergoing COH using GnRH-antag COH protocols, should dictate embryo cryopreservation and cancelation of the fresh transfer, in those undergoing the GnRH-ag COH protocol, a fresh embryo transfer should be recommended.

GnRH-agonist ovulation trigger in patients undergoing controlled ovarian hyperstimulation for IVF with ultrashort flare GnRH-agonist combined with multidose GnRH-antagonist protocol.

OBJECTIVE: To evaluate, whether Gonadotropin-releasing hormone-agonist (GnRH-agonist or GnRH-ag) trigger in patients undergoing the ultrashort GnRH-ag/GnRH-antagonist (GnRH-ant) protocol is as effective as in patients at high risk to develop severe ovarian hyperstimulation syndrome (OHSS), who undergo the multidose GnRH-ant protocol. DESIGN: Cohort study. SETTING: University hospital. PATIENTS: All consecutive women aged ≤35 years admitted to our IVF unit from January 2011 to October 2011 who reached the ovum pick-up stage. INTERVENTIONS: Triggering final oocytes maturation by GnRH-ag instead of hCG, in high-responder patients undergoing either the ultrashort GnRH-ag/GnRH-ant or the multidose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocols. MAIN OUTCOME MEASURES: Ovarian stimulation characteristics, percentage of mature oocytes, fertilization and pregnancy rates. RESULTS: No inbetween groups differences were observed in ovarian-stimulation related variable, percentage of mature oocytes, fertilization or pregnancy rates. No case of moderate-severe OHSS was reported in the study, or the control groups. CONCLUSIONS: Three consecutive doses of daily GnRH-ag administration at the beginning of ultrashort flare GnRH-ag/GnRH-ant COH protocol, did not interfere with the ability of the GnRH-ag to trigger final oocytes maturation at the end of the COH cycle.

Does day-3 LH/FSH ratio influence in vitro fertilization outcome in PCOS patients undergoing controlled ovarian hyperstimulation with different GnRH-analogue?

In an attempt to evaluate whether high basal day-3 luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio affects IVF cycle outcome in polycystic ovary syndrome (PCOS) patients undergoing ovarian stimulation with either GnRH-agonist (n = 47) or antagonist (n = 104), we studied 151 IVF cycles: 119 in patients with basal LH/FSH <2 and 32 in patients with LH/FSH ≥ 2. The PCOS with high LH/FSH ratio achieved a non-significantly higher pregnancy rate using the GnRH-agonist (50% vs 17.9%, p = 0.2; respectively), as compared to the GnRH-antagonist protocols, probably due to the ability of the long GnRH-agonist protocol to induce a prolong and sustained reduction of the high basal LH milieu and avert its detrimental effect on oocyte quality and implantation potential.

A combined approach to patients with repeated IVF failures.

In an attempt to evaluate the appropriate approach in patients with repeated IVF failures, we compared the stimulation characteristics of 19 cycles. This includes the combination of diagnostic hysteroscopy and endometrial sampling during oral contraceptive pill treatment, which precedes the ultrashort GnRH-ag/GnRH-ant protocol to the patients' previous failed IVF attempt. Patients undergoing the combined approach achieved an improved outcome with reasonable implantation and clinical pregnancy rates (25 and 42%, respectively).

Ovarian stimulation in polycystic ovary syndrome patients: the role of body mass index.

In an attempt to examine whether body mass index (BMI) may influence IVF outcome in polycystic ovary syndrome (PCOS) patients undergoing ovarian stimulation with either gonadotrophin-releasing hormone (GnRH)-agonist (agonist group) or antagonist (antagonist group), 100 IVF cycles were studied: 35 in the agonist and 65 in the antagonist groups. In both agonist and antagonist groups, patients with BMI < or = 25 kg/m(2) had a significantly higher fertilization rate compared with patients with BMI > 25 kg/m(2) (P < 0.02 and P < 0.01, respectively). Lean patients (BMI < or = 25) undergoing ovarian stimulation using the GnRH-agonist, demonstrated the highest pregnancy rate. In conclusion, in this series of PCOS patients undergoing IVFembryo transfer cycles, ovarian stimulation utilizing the midluteal long GnRH-agonist suppressive protocol yielded a higher pregnancy rate in lean patients, probably due to its ability to lower the high basal LH milieu and its detrimental effect on oocyte quality and implantation potential.

HMG improves IVF outcome in patients with high basal FSH/LH ratio: a preliminary study.

In an attempt to examine the role of human menopausal gonadotrophin (HMG) administration in patients with high basal FSH/LH ratio, patients undergoing at least two IVF cycles, where one included HMG (HMG group) and the other included recombinant FSH (rFSH) only (FSH group), were studied. The use of HMG, in this specific group of patients, produced significantly higher number of top-quality embryos (3.9 +/- 3.1 versus 2.5 +/- 1.7, respectively; P < 0.05), higher implantation (27.9% versus 5.3%, respectively; P +/- 0.003) and clinical pregnancy rates (44.4% versus 11.1%, respectively; P < 0.02), as compared with rFSH. Moreover, while the HMG group achieved a significantly higher peak oestradiol concentration (P = 0.04), no differences were observed between the groups in the other ovarian stimulation variables. In conclusion, the use of HMG in patients with high basal FSH/LH ratio, produced significantly higher number of top-quality embryos, and higher implantation and clinical pregnancy rates, compared with rFSH.

What is the preferred GnRH analogue for polycystic ovary syndrome patients undergoing controlled ovarian hyperstimulation for in vitro fertilization?

In an attempt to evaluate the influence of the GnRH analogue used during controlled ovarian hyperstimulation (COH) on the outcome of IVF cycles of polycystic ovary syndrome (PCOS) patients, we studied 152 IVF cycles. The PCOS patients undergoing COH using the GnRH agonist protocol (n = 50) showed a significantly higher pregnancy rate (36% vs. 19.6%, respectively), compared with the GnRH antagonist protocol (n = 102).

Follitropin-alpha (Gonal-F) versus follitropin-beta (Puregon) in controlled ovarian hyperstimulation for in vitro fertilization: is there any difference?

In an attempt to examine and compare the effect of the two commercially available recombinant FSH on ovarian stimulation characteristics and IVF cycle outcome, we studied 264 IVF cycles in patients with a favorable prognosis a priori, 198 in patients using follitropin-alpha, and 68 in patients using follitropin-beta. Although both groups achieved a comparable number of retrieved oocytes, the use of follitropin-beta was associated with a tendency toward a lower clinical pregnancy rate (PR), and with significantly higher E(2) levels despite the use of significantly lower total gonadotropin dose.

Ultrashort flare GnRH agonist combined with flexible multidose GnRH antagonist for patients with repeated IVF failures and poor embryo quality.

To evaluate the appropriate controlled ovarian hyperstimulation (COH) protocol in patients with repeated IVF failures and poor embryo quality we compared the stimulation characteristics of ten cycles which included ultrashort flare GnRH agonist combined with flexible multidose GnRH antagonist with the patients' earlier failed IVF attempts. The use of ultrashort GnRH agonist/GnRH antagonist COH protocol resulted in a significantly higher number and proportion of top-quality embryos, with a consequent improvement in clinical pregnancy rate (50%).

Does day 3 luteinizing-hormone level predict IVF success in patients undergoing controlled ovarian stimulation with GnRH analogues?

To examine whether day 3 LH level or FSH-LH ratio predict IVF outcome, we studied patients with a favorable prognosis a priori undergoing controlled ovarian hyperstimulation (COH) with GnRH agonist (agonist group; n = 131) or antagonist (antagonist group; n = 137). Although LH level could not predict IVF outcome, patients undergoing COH using the GnRH antagonist or agonist protocols with FSH-LH ratios >2 or >3, respectively, achieved significantly lower pregnancy rates (11.1% vs. 27.7% and 8.3% vs. 31.9%, respectively).

GnRH agonist versus GnRH antagonist in ovarian stimulation: the role of endometrial receptivity.

To examine whether the choice of the GnRH analogues used during controlled ovarian hyperstimulation (COH), may influence endometrial receptivity, we studied 712 IVF cycles, in patients undergoing COH with GnRH agonist or antagonist and with the transfer of at least one top-quality embryo. The GnRH agonist group showed significantly higher endometrial thickness and higher pregnancy rate, suggestive of a higher endometrial receptivity, compared with the GnRH antagonist group.

Tofupill/Femarelle (DT56a): a new phyto-selective estrogen receptor modulator-like substance for the treatment of postmenopausal bone loss.

OBJECTIVE: To evaluate the efficacy of Tofupill/Femarelle (DT56a), a novel phyto-selective estrogen receptor modulator (SERM), in preserving bone mineral density (BMD) in postmenopausal women. DESIGN: The study sample consisted of 98 healthy, postmenopausal women who were randomly allocated, on a double-blind basis, to receive either 644 mg/d DT56a (study group) or 344 mg/d DT56a supplemented with calcium (low-dose group) for 12 months. Each participant was assessed with a comprehensive health questionnaire, a detailed physical, and laboratory and pelvic sonogram examinations at entry and every 3 months thereafter. BMD was assessed by dual-energy x-ray absorptiometry (Lunar) of the lumbar spine and femoral neck before the study began and after 12 months of treatment. RESULTS: After 12 months of treatment, BMD had increased in the study group by 3.6% in the lumbar spine (P = 0.039) and by 2.0% in the femoral neck (NS). In the low-dose group, BMD had decreased in the lumbar spine by 0.6% (NS) and by 0.6% in the femoral neck (NS). Comparison of the change in bone density between the groups yielded a significant difference for the lumbar spine (P = 0.037). Neither group showed a change in endometrial thickness and sex hormone levels nor reported any side effects of treatment. CONCLUSIONS: Tofupill treatment in postmenopausal women increases BMD without unwanted estrogenic effect. Tofupill appears to be a promising phyto-SERM for the prevention of postmenopausal osteoporosis.