The impact of unilateral oophorectomy on ovarian reserve in assisted reproduction: a systematic review and meta-analysis.

BACKGROUND: Women following unilateral oophorectomy (UO) are occasionally encountered during assisted reproduction treatment. OBJECTIVE: To explore the impact of UO on ovarian reserve in assisted reproduction. SEARCH STRATEGY: An electronic database search was performed using PubMed, EBSCO, ISI, Trip, ClinicalTrial.gov and the Cochrane library followed by a manual search to identify published research between January 1978 and December 2015. SELECTION CRITERIA: Controlled studies that compared infertile women following UO undergoing IVF-ET treatment with women with two intact ovaries. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data concerning the impact of UO on ovarian reserve tests, ovarian response to controlled ovarian hyperstimulation and clinical pregnancy rate. Meta-analysis was performed using these measures. MAIN RESULTS: Twenty-one studies were eligible for quantitative analysis. They included 1045 and 18 172 IVF cycles in women with one and two intact ovaries, respectively. Basal FSH weighted mean difference (WMD) was significant (2.01 IU/l; 95% CI: 0.24-3.79, P = 0.026). Similarly, the WMD of serum E2 level on the day of hCG administration was significant (WMD: -431 pg/ml; 95% CI: -616 to -246, P < 0.001). However, the weighted overall odds ratio (OR) of clinical pregnancy between women with a single ovary and women with two ovaries was comparable (overall OR: 0.76; 95% CI: 0.57-1.00, P = 0.054). All eligible studies were retrospectively conducted and the heterogeneity among ovarian response measures was high. CONCLUSIONS: Available pooled data supports an adverse effect of UO on ovarian reserve involving the quantity but not the quality of the ovarian pool. TWEETABLE ABSTRACT: Review finds women with one ovary removed have less IVF capacity but the same pregnancy rate as women with two ovaries.

The effect of rLH supplementation to the GnRH-antagonist protocol on endocrine dynamics in the advanced reproductive age.

PURPOSE: To explore serum endocrine dynamics, specifically LH levels, following rLH supplementation to rFSH following GnRH-antagonist treatment in the advance reproductive age. METHODS: Women were prospectively and similarly treated employing rFSH and the flexible GnRH-antagonist protocol, while rLH was supplemented only to the study group. Serum FSH, LH, E2, and P were evaluated throughout the follicular phase. Three strategies were a priori planned to examine endocrine dynamics among women enrolled. RESULTS: While serum LH drop were similar before GnRH-antagonist stimulation, it dropped more times in the control group compared to the study group. Among women receiving rFSH only, serum LH levels dropped ≤2, ≤1 and ≤0.5 mIU/mL in 71.4, 46.4, and 28.6% of cases, while this occurred only in 38.7% (P = 0.01), 6.5% (P = 0.0004) and 3.2% (P = 0.007) of women receiving combined rFSH and rLH treatment, respectively. The same trend was found when serum LH dropped in at least two occasions following the GnRH-antagonist administration. Conversely, serum LH diagrams throughout the follicular phase did not differ between the two groups. Furthermore, individual area under the curve values of LH, E2, and P was similar between the two groups following GnRH-antagonist initiation. CONCLUSIONS: Different strategies to explore LH dynamics following the GnRH-antagonist administration have resulted in diverse results, implying the need for a consensus definition of LH threshold for adequate folliculogenesis and steroidogenesis. Such action would pave the way for understanding which groups of patients may benefit from rLH supplementation.

Reverse breech extraction in cases of second stage caesarean section.

Our objective was to examine the feasibility of reverse breech extraction to disengage fetal head from the pelvis at second stage caesarean section (CS). A total of 50 consecutive women with singleton term pregnancies undergoing urgent CS at second stage were retrospectively evaluated. A total of 29 were delivered by the reverse breech manoeuvre (study group) and 21 women were delivered by the conventional approach (control group). The reverse breech extraction was successful in all cases of the study group. The mean estimated blood loss during operation, haemoglobin drop, Apgar scores at 1 and 5 min as well as cord PH were similar between the groups. The mean newborn weights were similar, 3492 ± 426 and 3610 ± 392 g in the study and control group, respectively. One case of an inadvertent extension of the low transverse incision was encountered in each group. Also, in three cases of the study group the incision was intentionally extended to an inverted T-shape to facilitate the manoeuvre. None of the newborns in both groups had trauma related to the extraction or were admitted to the neonatal intensive care unit. All women following CS had a low rate complication rate in the postpartum period. We conclude that reverse breech extraction seems to be feasible to disengage fetal head from the pelvis at second stage CS. Maternal and newborn complications following this manoeuvre seem to be low.

Ovarian aging and implications for fertility female health.

Ovarian aging is a major detrimental factor of pregnancy achievement and it is related to other issues of women's health. The purpose of this review is to present an update on ovarian aging risk factors followed by contemporary methods of its assessment and an overview of its current management strategies in assisted reproductive technologies (ART). Ovarian aging is a multifactorial trait governed by several factors including medical, lifestyle, genetic, autoimmune and idiopathic. There are several established risk factors and many others that are still being revealed. Heritability has a major influence on ovarian aging. Different genetic strategies and approaches for ovarian aging evaluation have been rapidly expanding; however the mission is far from complete. Genome-wide association studies seems to be the most applicable to advance this research. Although anti-Müllerian hormone and antral follicle count (AFC) biomarkers seems to be the most reliable predictors of ovarian aging, none has demonstrated conclusive evidence to predict pregnancy achievement in an ART setting. The debate continues which of the two predictors is the most suitable in ART as well as non-ART settings. Although multivariate models have been shown to be equally predictive to AFC, latest data support the notion that chronological age and genetic markers inclusion may increase their reliability. Several strategies have been suggested to manage ovarian aging in ART settings. None of the stimulation protocols or ART interventions has been shown to be convincingly beneficial to ovarian aging women and individualization of treatment is still recommended. Ovarian priming by different androgen preparations has been shown to be promising but more randomized controlled studies are required to substantiate these findings. Except for oocyte donation other ART strategies have not shown a persuasive evidence for advanced ovarian aging infertility patients. The new development of oocyte vitrification may well introduce opportunities for fertility preservation to woman at risk. It is concluded that proper assessment and detection of ovarian aging, employing current or developing biomarkers of ovarian reserve, may enable health providers to recommend, at appropriate biological time, early pregnancy achievement or fertility preservation in women at risk.

Increased progesterone/estradiol ratio in the late follicular phase could be related to low ovarian reserve in in vitro fertilization-embryo transfer cycles with a long gonadotropin-releasing hormone agonist.

OBJECTIVE: To gain insight into the physiologic as well as the clinical significance of premature luteinization in the long gonadotropin-releasing hormone agonist (GnRH-a) cycles and to evaluate whether it may be a manifestation of low ovarian reserve. DESIGN: Prospective evaluation. SETTING: A university-affiliated reproductive medicine unit. PATIENT(S): Seventy-six consecutive infertile women. INTERVENTION(S): The long GnRH-a protocol was used for IVF-ET treatment. MAIN OUTCOME MEASURE(S): Women in the study were prospectively evaluated in their first cycle of treatment and were divided into those with (study group) or without premature luteinization (control group). Premature luteinization was defined as P/E2 ratio of more than 1 on the day of hCG administration. RESULTS(S): Thirty-one (41%) of the women in the study demonstrated premature luteinization. Patients' characteristics were comparable between the two groups. Late follicular P/E2 ratio was significantly and considerably higher in the study as compared to the control group, 2.4 +/- 1.7 and 0.7 +/- 0.2, respectively. Ovarian reserve parameters including day 3 FSH, E2 level on hCG day, total amount of hMG, number of follicles, oocytes, and embryos were significantly inferior in the study as compared to the control group. P levels on hCG day were significantly higher in the study as compared to the control group, 1.9 +/- 0.7 ng/mL and 1.2 +/- 0.6 ng/mL, respectively. However, LH levels on hCG day did not differ between the groups, 1.4 +/- 0.7 mIU/mL and 1.2 +/- 0.7 mIU/mL, respectively. The clinical pregnancy rate was significantly lower in the premature luteinization group as opposed to controls, 13% and 42%, respectively. CONCLUSION(S): Premature luteinization, defined as late follicular P/E2 >1, in long GnRH-a cycles seems to adversely affect clinical outcome. Our findings in this setting support the notion that premature luteinization could be related to low ovarian reserve and that this manifestation is not necessarily an LH-dependent event.

Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin.

Inherited and acquired thrombophilia are associated with recurrent pregnancy loss (RPL). We have evaluated the efficacy and safety of the low molecular weight heparin enoxaparin in 50 women, (mean age 26 +/- 3 years) with RPL (> or =3 losses in 1st, > or =2 losses in 2nd and > or =1 loss in 3rd trimester) who were found to harbor thrombophilia. Twenty-seven had a solitary thrombophilic defect, and twenty-three women had combined thrombophilic defects: 17--two defects and 6--three defects. Following diagnosis of thrombophilia, sixty-one subsequent pregnancies were treated with the low molecular weight heparin enoxaparin throughout gestation until 4 weeks after delivery. Dosage was 40 mg/day in women with solitary defect and 80 mg/day in combined defects. Aspirin, 75 mg daily was given in addition to enoxaparin to women with antiphospholipid syndrome. Forty-six out of 61 (75%) gestations treated by enoxaparin resulted in live birth compared to only 38/193 (20%) of the untreated pregnancies in these 50 women prior to diagnosis of thrombophilia (p <0.00001). In 23 women without a single living child following 82 untreated gestations, antithrombotic therapy resulted in 26/31 (84%) successful deliveries (p <0.0001). In 20 women with a prior living child, antithrombotic therapy improved successful delivery from 33/86 (38%) to 20/21 (95%) (p <0.0001). Enoxaparin dose of 40 mg/day resulted in live birth in 24/35 (69%) of gestations, compared to 19/23 (83%) gestations in women treated with 80 mg/day (p = 0.37). Only one thrombotic episode and one mild-bleeding episode were noticed during enoxaparin therapy. Enoxaparin is safe and effective in prevention of pregnancy loss in women with inherited and acquired thrombophilia.

The effect of thrombophylaxis on pregnancy outcome in patients with recurrent pregnancy loss associated with factor V Leiden mutation.

OBJECTIVE: To observe the effect of thrombophylaxis on pregnancy in women with a history of unexplained recurrent pregnancy loss also carrying the factor V Leiden mutation. METHODS: Between 1 January and 31 December 1996, activated protein C (APC) resistance and factor V Leiden mutation were prospectively measured in 56 nonpregnant women, with a history of two or more unexplained recurrent pregnancy losses. During the same study period, seven women carrying the factor V Leiden mutation conceived, and were subsequently followed throughout their pregnancy. Subcutaneous low molecular weight heparin (LMWH, enoxaparin, 40 mg/day) and oral low dose aspirin (100 mg/day) were administered throughout the pregnancies, starting at early first trimester. Ultrasound and Doppler umbilical and fetal middle cerebral arterial flow studies were performed in the second and third trimesters, and the course and outcome of the pregnancies were documented. RESULTS: Activated protein C resistance and factor V Leiden were found in 20 (36%) and 12 (21%) women of the study, respectively. Five of the seven pregnancies occuring progressed uneventfully to term with normal fetal growth, normal Doppler flow studies and uneventful neonatal outcome. Two of the seven women had early missed abortions. CONCLUSIONS: Thrombophylaxis, beginning in early pregnancy, in women with unexplained recurrent pregnancy loss associated with factor V Leiden mutation, seems to be safe and allow normal fetal development and good neonatal outcome. To prove the efficacy of thrombophylaxis by LMWH and low dose aspirin in this setting prospective controlled studies seem to be justified.

Activated protein C resistance and factor V Leiden mutation can be associated with first-as well as second-trimester recurrent pregnancy loss.

PROBLEM: To examine whether the occurrence of activated protein C resistance (APCR) and factor V Leiden mutation differs in women with first- compared to women with second-trimester unexplained recurrent pregnancy loss. METHOD OF STUDY: Seventy eight consecutive women with two or more unexplained post-embryonic recurrent pregnancy losses and 139 fertile women with at least one successful pregnancy and no abortions were prospectively investigated for APCR and the factor V Leiden mutation. No women were pregnant at the time of investigation. APCR was defined as APC sensitivity ratio (APC SR) of < or = 2.0. All patients with an APC SR < or = 2.4 were investigated for the factor V Leiden mutation. Women in this study were divided into three groups. Group A included only women with a history of recurrent first-trimester embryonic loss (37 women) and Group B included women with second-trimester abortions with or without additional first-trimester abortions (41 women). Group C included the controls (139 women). RESULTS: APCR and factor V Leiden mutations were significantly more prevalent in all recurrent pregnancy loss patients in this study as compared to controls. 38%(30/78) and 19%(15/78) in contrast to 8% (11/139) and 6% (8/139), respectively. All three groups in the study were comparable regarding age, parity, and number of living children, whereas Groups A and B were also comparable regarding gravidity. Mean APC SRs were significantly higher in Group C as compared to Groups A and B. The incidence of APCR was significantly higher in Groups A and B, as compared to controls, 27 and 49% in contrast to 8%, respectively. Moreover, the incidence of the factor V Leiden mutation was significantly higher in Groups A and B as compared to Group C, 16 and 22% as distinct from 6%, respectively. The incidence of APCR was higher in Group B as compared to Group A, 49% in contrast to 27%, with borderline significance: however, the factor V Leiden mutation did not significantly differ between the two groups. CONCLUSIONS: APCR and factor V Leiden are associated with unexplained recurrent pregnancy loss. The occurrence of APCR and factor V Leiden seems to be linked to post-embryonic first-trimester as well as second-trimester recurrent pregnancy loss. The significance of acquired, non-heritable APCR in recurrent fetal loss patients, especially in the second-trimester aborters, is still to be determined.

Premature luteinization: could it be an early manifestation of low ovarian reserve?

OBJECTIVE: To gain insight into the physiologic significance of premature luteinization and to evaluate whether it could be a manifestation of low ovarian reserve. DESIGN: Retrospective evaluation. SETTING: Reproductive medicine unit. PATIENT(S): Thirty-one consecutively seen women with normal ovulation and unexplained infertility. INTERVENTION(S): Induction of superovulation with hMG coupled with synchronized IUI. A GnRH agonist was not used during the study. MAIN OUTCOME MEASURE(S): Premature luteinization was defined as a progesterone/estradiol ratio of > 1 on the day of hCG administration. Patients were evaluated during their first cycles of hMG treatment and then were divided into those with (study group) and those without (control group) premature luteinization. The ovarian reserve parameters were compared between the two groups. RESULT(S): Nineteen of the 31 patients with unexplained infertility demonstrated premature luteinization. Patient characteristics were similar between the study and control groups. Mean (+/- SD) day 3 FSH levels were 8.2 +/- 3.3 and 6.6 +/- 1.7 mIU/mL in the study and control groups, respectively. Mean (+/- SD) day 3 estradiol levels were significantly higher in the study than in the control group (74 +/- 49 pg/mL vs. 30 +/- 17 pg/mL, respectively). Mean (+/- SD) estradiol levels on the day of hCG administration also differed significantly between the study and control groups (760 +/- 539 pg/mL vs. 1,568 +/- 675 pg/mL, respectively). Likewise, the number of follicles that were > or = 15 mm on the day of hCG administration was significantly lower in the study than in the control group (2.9 +/- 1.5 vs. 4.3 +/- 1.3, respectively). The total dose of hMG and duration of administration were similar in the two groups. The clinical pregnancy rates after four cycles of treatment were 15.8% and 41.7% in the study and control groups, respectively. CONCLUSION(S): This preliminary work suggests that, in cycles that are not treated with a GnRH agonist, signs of premature luteinization in patients with unexplained infertility could be an early manifestation of low ovarian reserve. It appears that hMG treatment in this group of patients could uncover the pathogenesis of their infertility.

Late manifestation of pelvic abscess following oocyte retrieval, for in vitro fertilization, in patients with severe endometriosis and ovarian endometriomata.

PURPOSE: Our purpose was to study the unusual and rare late manifestation of severe pelvic abscess, following oocyte pickup (OPU), for in vitro fertilization and embryo transfer (IVF-ET). PATIENTS: The patients were three infertile women with stage IV endometriosis and ovarian endometriomata, as the sole reason for their infertility. Medical and surgical modalities to treat endometriosis and infertility proved to be unsuccessful. INTERVENTIONS: All patients were prepared for IVF-ET employing a long GnRH-a and hMG protocol. Transvaginal OPU was performed under ultrasound guidance. Intravenous (i.v.) prophylactic antibiotic was routinely administered. RESULTS: All women underwent ET, and one conceived. Forty, 24, and 22 days after OPU, respectively, these patients presented with acute symptoms of severe pelvic inflammatory disease (PID) and were found to have pelvic abscess. Broad-spectrum i.v. antibiotics were employed in all cases, however, two patients did not respond and bilateral adnexectomy was eventually performed. CONCLUSIONS: Severe endometriosis with ovarian endometriomata seems to be a significant risk factor for pelvic abscess development, following transvaginal OPU for IVF-ET. Prophylactic IV cefazolin does not seem to prevent this complication. Late manifestation of pelvic abscess supports the notion that the presence of old blood in an endometrioma provides a culture medium for bacteria to grow slowly after transvaginal inoculation.

Endometrial preparation: lessons from oocyte donation.

OBJECTIVE: To gain insight into the physiology of human endometrial development after artificial preparation with estrogen (E) and P, before oocyte donation. DESIGN: Review and analysis of relevant studies published in the last decade, identified through the literature and Medline searches. RESULTS: Oocyte donation represents a unique in vivo experimental model in the human that permits the study of endometrial development under controlled variable conditions. Early studies have shown that adequate endometrial preparation can be achieved by sequential E and P only. The successful implementation of the simplified approach to oocyte donation demonstrated that satisfactory endometrial receptivity is not dependent on incremental administration of E and P and similarly can be achieved by fixed dosages of these steroids. Moreover, numerous clinical oocyte donation studies have shown that both physiologic and supraphysiologic levels of E and P have resulted in good endometrial development and pregnancy rates, underlining the relative insensitivity of the endometrium to extreme hormonal conditions. In addition, it has been clarified that the endometrium is tolerant of some manipulations during the follicular phase. Contrary to morphological studies that demonstrated preservation of endometrial preparation after luteal E depletion, preliminary evidence suggests that the functional capacity of the endometrium could be affected adversely. CONCLUSION: In contrast to early oocyte donation studies, which indicated a correlation between morphologic integrity and functional capacity of the endometrium, some evidence presented in this review demonstrates that adequate endometrial morphology does not always imply normal endometrial receptivity.

Double-layer closure of uterine incision with visceral and parietal peritoneal closure: are they obligatory steps of routine cesarean sections?

The objective of this study was to examine the feasibility of a modified technique of cesarean section in which the uterine incision is sutured in one layer and the visceral and parietal peritoneum are left open. Two hundred patients undergoing a low segment cesarean section were prospectively randomized (according to the patients' identity numbers) into two groups. The first group had standard cesarean section including a continuous double layer closure of uterine incision in addition to closure of visceral and parietal peritoneum. The second group underwent the modified procedure as described above. The modified technique compared to the standard technique, resulted in shorter operative time (32 +/- 11 versus 44 +/- 16 min, P < 0.0001) and a reduced need for postoperative sedation (P < 0.004). The operative procedure was shown, by multiple regression analysis, to be the significant factor that determined its length. Postoperative morbidity was similar in the two groups. The modified technique of cesarean section reduces operative time and postoperative narcotic requirement, and has no adverse affect on postoperative recovery. A double-layer closure of low uterine incision, re-approximation of bladder flap, and closure of parietal peritoneum, as in the standard technique, do not seem to be essential steps of cesarean section. Larger studies are needed to ensure the safety of one-layer uterine closure in future deliveries.

The effect of estradiol depletion during the luteal phase on endometrial development.

OBJECTIVE: To examine whether luteal E2 is obligatory for obtaining an adequately developed endometrium. DESIGN: Survey of women with premature ovarian failure (POF) in a prospective, controlled, randomized study. SETTING: In vitro fertilization unit in a tertiary care university medical center. PATIENTS: Fourteen amenorrheic women with POF, candidates for oocyte donation, were divided into two distinct groups with seven women in each subgroup. INTERVENTIONS: Endometrial priming with a fixed dose of oral micronized E2, 4 mg/d for 14 days, was similarly performed in the study and the control groups. Progesterone replacement during the luteal phase was also identical in the two groups and was accomplished by IM P in oil, 50 mg/d for another 14 days. Only the control group continued to have the same E2 regimen during the luteal phase. MAIN OUTCOME MEASURES AND RESULTS: Follicular phase mean E2 levels as well as luteal phase mean P levels were similar in both groups. However, luteal E2 levels differed significantly between the study and the control groups (21 +/- 5 and 692 +/- 199 pg/mL, respectively; conversion factor to SI units, 3.671). Nevertheless, histologic evaluation of endometrial biopsies on days 21 and 26 were similar for both groups. Endometrial gland dating, using light microscopy in the study and the control groups, on day 21, was 19.1 +/- 0.8 and 18.4 +/- 0.5, respectively, and on day 26, 25.4 +/- 0.8 and 25.9 +/- 0.5, respectively. Dating of the stroma in the two biopsies was also similar in both groups. Moreover, transmission electron microscopy performed in two patients of the study group showed typical characteristics of a secretory endometrium. CONCLUSIONS: Luteal E2 depletion in the human does not seem to adversely affect the morphological developmental capacity of the endometrium. Our results suggest that E2 secretion by the corpus luteum in the human does not appear to be obligatory for the development of a normal secretory endometrium. The actual receptivity of the endometrium after such preparation needs to be evaluated.

The effect of progesterone administration in the follicular phase of an artificial cycle on endometrial morphology: a model of premature luteinization.

OBJECTIVE: To evaluate the effect of premature P administration on artificially prepared endometrium in women with ovarian failure. DESIGN: To mimic premature luteinization, patients with ovarian failure were treated with continuous estrogen and episodic P during the follicular phase of artificial cycles. SETTING: In vitro fertilization unit at a university hospital. PATIENTS: The study group included 16 patients with ovarian failure who were randomly divided into two groups. Group A (8 patients) was treated by episodic P administration during the artificial follicular phase on days 2 and 7 (12.5 mg of P in oil IM), and in group B (8 patients), P (6.25 mg) was added on days 3, 4, and 5. Another 16 patients (group C), age matched to the study group, were arbitrarily allocated to serve as controls and had standard preparatory cycles without P supplementation in the follicular phase. Serum E2 and P levels and endometrial biopsies were taken on days 14 and 26. RESULTS: Serum E2 levels were comparable between the study group (group A+B) and controls on both days 14 and 26. Although serum P levels did not differ between the groups on day 26, it was higher in the follicular phase of the study group than in the controls (1.9 +/- 4.0 and 0.2 +/- 0.1 ng/mL, respectively). In the study group, 8 of 16 patients demonstrated early secretory changes in the late follicular phase biopsies, and 9 of 16 women developed stromal-glandular discrepancy in the late luteal phase. This differed significantly from the controls in which only one late luteal biopsy was out of phase. CONCLUSIONS: Episodic surges of P during the follicular phase may result in impaired endometrial development that cannot be corrected by P supplementation during the luteal phase. This unique model provides evidence for the potential detrimental effect of premature P secretion in the follicular phase on endometrial function.

The effect of growth hormone on granulosa cell function during in-vitro fertilization.

The effect of growth hormone addition to human menopausal gonadotrophin (HMG), after pituitary down-regulation, on granulosa cell function, in in-vitro fertilization (IVF) was evaluated. Growth hormone or placebo were added in a prospective, randomized and double-blind manner to an existing IVF stimulation protocol. Forty-two normal ovulatory women (< or = 38 years old) with mechanical factor infertility and normal male factor were included in the study. Gonadotrophin-releasing hormone agonist (GnRHa) was given from day 21 of the previous cycle until human chorionic gonadotrophin (HCG) administration. Follicular stimulation with HMG was started after pituitary down-regulation. Growth hormone 12 IU/day or placebo were administered on alternate days, beginning day 1 until day 7 of HMG treatment. Granulosa cell function was evaluated, in all patients, by follicular fluid levels of ovarian steroids and insulin-like growth factor-I (IGF-I). In 14 patients, chosen arbitrarily granulosa lutein cells were cultured in the presence and absence of additional HCG. Follicular fluid levels of oestradiol, progesterone, testosterone and IGF-I were similar in both growth hormone and placebo groups. Basal and post-HCG levels of oestradiol and progesterone did not differ significantly between the two groups of granulosa lutein cell cultures. We conclude that after pituitary down-regulation, in-vivo administration of growth hormone with HMG in young ovulatory women does not seem to affect granulosa cell function when compared to the administration of HMG alone.

The effect of growth hormone supplementation on in vitro fertilization outcome: a prospective randomized placebo-controlled double-blind study.

OBJECTIVE: To determine the effect of growth hormone (GH) supplementation to a long gonadotropin-releasing hormone agonist (GnRH-a)/human menopausal gonadotropin (hMG) treatment protocol, on ovarian response, embryo quality, and clinical outcome in in vitro fertilization (IVF). DESIGN: Growth hormone or placebo were administered in a prospective randomized double-blind manner. PATIENTS: Forty-two normal ovulatory, women who were 38 years of age or less with mechanical factor infertility and a normal male factor were selected for this study. INTERVENTIONS: Gonadotropin-releasing hormone agonist, 0.5 mg/d, was initiated in the midluteal phase of the preceding cycle and continued until the day of human chorionic gonadotropin (hCG) administration. Ovulation induction with hMG was started 14 days after pituitary down regulation (17 beta-estradiol [E2] serum level less than 30 pg/mL). Growth hormone (12 IU/d) or placebo were administered on days 1, 3, 5, and 7 of hMG treatment. RESULTS: Breaking the code at the completion of the study revealed that 20 women received GH and 22 placebo. The age and duration of infertility did not differ between the two groups. Follicular phase duration, hMG ampules used, serum E2, and number of follicles (greater than or equal to 14 mm) on day of hCG as well as number of oocytes and embryos achieved were similar in both groups. Embryo morphology and rate of cleavage were also similar. Insulin-like growth factor-I (IGF-I) serum levels did not change after pituitary down regulation and increased significantly both after GH/hMG and placebo/hMG ovulation induction treatment. Clinical pregnancy rate (PR) per embryo transfer and implantation rate were 40% versus 32% and 17.9% versus 11.3% in the GH and placebo groups, respectively, and were not statistically different. CONCLUSIONS: In normo-ovulatory women undergoing ovulation induction for IVF, GH supplementation to hMG after GnRH-a pituitary down regulation does not seem to augment ovarian response or improve embryo quality. The effect of this regimen on actual PRs and implantation rates needs further clarification.