<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03773263</url>
  </required_header>
  <id_info>
    <org_study_id>newivf20181206</org_study_id>
    <nct_id>NCT03773263</nct_id>
  </id_info>
  <brief_title>New Application of Sequential in Vitro Muturation System for Infertility Patients With Polycystic Ovary Syndrome</brief_title>
  <official_title>New Application of Oocyte Sequential Culture and in Vitro Muturation System for Infertility Patients With Polycystic Ovary Syndrome: a Multi-center Prospective Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital for Reproductive Medicine Affiliated to Shandong University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital with Nanjing Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First Affiliated Hospital of Wenzhou Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shanghai 10th People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Oocyte in vitro maturation (IVM) is an artificial reproductive technologies (ART) in which&#xD;
      cumulus-oocyte complex (COC) are collected at the immature germinal vesicle (GV) stage from&#xD;
      unstimulated or FSH-primed ovaries and matured in vitro before fertilization. IVM has been&#xD;
      proposed as a more patient-friendly ART alternative to conventional IVF. Contrary to IVF, IVM&#xD;
      is the only ART method with no cases of OHSS reported. Hence, patients with PCOS represent&#xD;
      the major target population for IVM treatment.&#xD;
&#xD;
      In clinical practice of standard IVM, COCs are aspirated from unstimulated or mildly&#xD;
      stimulated ovaries and rapidly removed from the meiotic-inhibiting influence of the follicle&#xD;
      and the follicular fluid. Regardless of in vitro gonadotrophin treatment, oocytes mature&#xD;
      spontaneously in vitro, hence undergoing meiotic resumption in the absence of the usual&#xD;
      elaborate cascade of endocrine and paracrine molecular signals that induce maturation in&#xD;
      vivo. As such, the maturation of oocytes by standard IVM techniques is an artefact that&#xD;
      compromises subsequent oocyte developmental competence. Numbers of studies have been proposed&#xD;
      to improve the efficiency of IVM system. Synchronization of meiotic and cytoplasmic&#xD;
      maturation in antral oocytes arrested at the immature GV-stage remains a major challenge and&#xD;
      is of fundamental importance for successful fertilization. High intra-oocyte levels of cyclic&#xD;
      adenosine monophosphate (cAMP), is crucial to maintain the nearly fully-grown oocytes under&#xD;
      meiotic arrest and to induce oocyte maturation. Research in animal models has indicated that&#xD;
      a non-physiological drop of cAMP levels in the oocyte results in asynchronous nuclear and&#xD;
      cytoplasmic maturation.&#xD;
&#xD;
      Investigators have reported the development of a novel in vitro simulated sequential oocyte&#xD;
      maturation system. Critical to success of the approach is a pre-IVM phase that generates a&#xD;
      rapid increase in COC cAMP levels. Secondly, the system utilizes an extended IVM phase&#xD;
      containing sufficient FSH to drive meiotic induction in the presence of a type-3 PDE&#xD;
      inhibitor. The high levels of cAMP in the oocyte and the induced nature of oocyte maturation&#xD;
      mimics some of the key, newly characterized molecular signals that occur during oocyte&#xD;
      maturation in vivo. Technical and conceptual elements were first developed using mouse,&#xD;
      bovine and human COCs. Investigators propose a randomized clinical trial to compare a novel&#xD;
      sequential culture system with the traditional standard oocyte IVM system for PCOS patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A multi-center, prospective, randomized clinical trial will be conducted, of comparing&#xD;
      sequential oocyte IVM system with traditional oocyte IVM system for high OHSS risk PCOS&#xD;
      patients (AMH&gt;5.6ng/ml). The inclusion criteria will be infertile patients diagnosed by the&#xD;
      Chinese PCOS criteria, aged below 35 years, and without other known factors interfere&#xD;
      reproductive or metabolic functions. 300 PCOS patients will be included and randomized into&#xD;
      either of two groups: group A will administrate sequential oocyte IVM system and group B will&#xD;
      administrate traditional standard oocyte IVM system. The comparison will be made between&#xD;
      groups, and both groups are conducted with the HMG administration and embryo vitrification&#xD;
      freezing. The primary outcome of the study is live birth rate. The embryo development and&#xD;
      pregnancy outcomes will be followed up and compared between groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">December 2018</start_date>
  <completion_date type="Anticipated">March 2020</completion_date>
  <primary_completion_date type="Anticipated">July 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical pregnancy rate</measure>
    <time_frame>7 weeks gestation</time_frame>
    <description>The fetal heart beat in an intrauterine gestational sac under ultrasound will be defined as clinical pregnancy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Oocyte maturation rate</measure>
    <time_frame>30 and 46 hours after oocyte retrieval</time_frame>
    <description>Oocyte maturation rate (%): number of MII oocytes/ number of oocytes retrieved.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fertilization rate</measure>
    <time_frame>30 and 46 hours after oocyte retrieval</time_frame>
    <description>Fertilization rate (%): number of oocytes fertilized/ number of oocytes retrieved.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cleavage rate</measure>
    <time_frame>24 hours after ICSI</time_frame>
    <description>Cleavage rate (%): number of cleavages/ number of 2PN embryos.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Day 3 embryo rate</measure>
    <time_frame>72 hours after ICSI</time_frame>
    <description>Day 3 embryo rate (%): number of Day 3 embryos / number of 2PN embryos.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Good quality embryo rate at cleavage-stage</measure>
    <time_frame>72 hours after ICSI</time_frame>
    <description>Good quality embryo rate at cleavage-stage (%): number of good quality embryos at cleavage-stage / number of 2PN embryos.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of cycles with available embryo</measure>
    <time_frame>72 hours after ICSI</time_frame>
    <description>Available embryos will be defined as three days after oocyte retrieval with containing more than 4 cells and grade 1 to 2 or containing 4 cells with a grade of 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blastulation rate</measure>
    <time_frame>144 hours after ICSI</time_frame>
    <description>Blastulation rate (%): number of blastocysts / number of 2PN embryos.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical pregnancy rate</measure>
    <time_frame>4 weeks gestation</time_frame>
    <description>A serum β-hCG level above 5 IU/L, which is performed 12 days after embryos transfer, will be defined as biochemical pregnancy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Implantation rate</measure>
    <time_frame>7 weeks gestation</time_frame>
    <description>The implantation rate will be defined as the number of gestational sacs seen on the ultrasound divided by the total number of embryos transferred.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Miscarriage rate (at first trimester)</measure>
    <time_frame>28 weeks gestation in maximum</time_frame>
    <description>Miscarriage at first trimester will be defined by any positive pregnancy test that result in a loss of pregnancy before 12 weeks gestation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative pregnancy rate</measure>
    <time_frame>1-2year</time_frame>
    <description>Cumulative pregnancy rate will be defined as clinical pregnancies with intrauterine fetal heart beat detected divided by the number of retrieval cycles whose embryos are all transferred.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preterm birth rate</measure>
    <time_frame>1-2year</time_frame>
    <description>Preterm birth means the baby is born before the 37th week of pregnancy in China.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Newborn birth weight</measure>
    <time_frame>1-2year</time_frame>
    <description>Newborn birth weight</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal complication rate</measure>
    <time_frame>within one month after labor</time_frame>
    <description>We will collect complications that occur in the neonate including admission to the neonatal intensive care unit (NICU), hospitalization, etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Live birth rate</measure>
    <time_frame>1-2year</time_frame>
    <description>Live birth rate(%): number of live birth/ transferred cycle.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Polycystic Ovary Syndrome</condition>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>sequential oocyte IVM group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>From day 7~9 of the menstrual cycle, 225 IU HMG (Menotrophins for Injection) per day will be administrated for 3 days. COCs were removed from aspirated follicular fluid and transferred into HEPES-buffered collection medium. The immature oocytes will be cultured in sequential IVM medium 1 for 6 hours (37℃, 5% CO2), and removed into sequential IVM medium 2 for further cultivation. After 24 and 40 hours cultivation, the mature oocytes will be fertilized by intracytoplasmic sperm injection (ICSI). Two of the D3 embryos (if available) which graded as top-quality embryo will be vitrified and the rest of embryos will be cultivated extendedly. Thawed embryo transfer (TET) will give preference to D3 embryos and carried out with a hormone replacement cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>traditional oocyte IVM group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>From day 7~9 of the menstrual cycle, 225 IU HMG (Menotrophins for Injection) per day will be administrated for 3 days. On the day of ovulation, COCs were aspirated and the immature oocytes will be cultured in traditional standard oocyte IVM system (Sage). 30 and 44 hours after cultivation, the maturity of oocytes will be assessed and the mature oocytes will be fertilized by intracytoplasmic sperm injection (ICSI). Two of the D3 embryos (if available) which graded as top-quality embryo will be vitrified and the rest of embryos will be cultivated extendedly. Thawed embryo transfer (TET) will give preference to D3 embryos and carried out with a hormone replacement cycle. If biochemical pregnancy is not achieved, thawed blastocysts transfer will be performed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sequential IVM system</intervention_name>
    <description>The immature oocytes will be cultured in sequential oocyte IVM medium 1 for 6 hours (37℃, 5% CO2). After flushed 3 times, COCs were removed into sequential oocyte IVM medium 2 for further cultivation.</description>
    <arm_group_label>sequential oocyte IVM group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>intracytoplasmic sperm injection (ICSI)</intervention_name>
    <description>intracytoplasmic sperm injection (ICSI)</description>
    <arm_group_label>sequential oocyte IVM group</arm_group_label>
    <arm_group_label>traditional oocyte IVM group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Thawed embryo transfer (TET)</intervention_name>
    <description>Patients administrates oestrogen (Progynova) 3mg twice a day for 10 to 12 days. From the day when endometrium reach a thickness of 8 mm and above, luteal phase support will be given with 10 mg progesterone (Dydrogesterone Tablets,) triple per day and utrogestan (Laboratories Besins International, Paris, France) 0.2g triple per day, until 14 days after embryo transfer.</description>
    <arm_group_label>sequential oocyte IVM group</arm_group_label>
    <arm_group_label>traditional oocyte IVM group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>traditional IVM system</intervention_name>
    <description>COCs were aspirated and the immature oocytes will be cultured in traditional standard oocyte IVM system (Sage). 30 and 44 hours after cultivation, the maturity of oocytes will be assessed.</description>
    <arm_group_label>traditional oocyte IVM group</arm_group_label>
    <other_name>sage</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women age ≤35 years;&#xD;
&#xD;
          2. AMH level ≥5.6ng/ml;&#xD;
&#xD;
          3. Women diagnosed as PCOS according to Chinese PCOS diagnosis criteria;&#xD;
&#xD;
          4. Written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who diagnosed as uterus abnormality, adenomyosis, submucous myoma, intrauterine&#xD;
             adhesion;&#xD;
&#xD;
          -  Women who diagnosed as untreated hydrosalpinx;&#xD;
&#xD;
          -  Women who had underwent unilateral ovariectomy;&#xD;
&#xD;
          -  Women with medical condition that represent contraindication to assisted reproductive&#xD;
             technology or pregnancy;&#xD;
&#xD;
          -  Women or their partner with abnormal chromosome karyotype;&#xD;
&#xD;
          -  Male partner with oligoasthenozoospermia or obstructive azoospermia;&#xD;
&#xD;
          -  Male partner whose sperm is collected by surgery;&#xD;
&#xD;
          -  Subjects are found breach the inclusion criteria, or in accordance with exclusion&#xD;
             criteria during the test, excluded;&#xD;
&#xD;
          -  Patients request withdrawal and exit the trial because adverse events occur during the&#xD;
             trial.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiao-yan Liang, M.D. &amp; Ph.D</last_name>
    <role>Study Director</role>
    <affiliation>The Sixth Affiliated Hospital, Sun Yat-Sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xiao-yan Liang, M.D. &amp; Ph.D</last_name>
    <phone>020-38048013</phone>
    <email>lxyzy@263.net</email>
  </overall_contact>
  <location>
    <facility>
      <name>The Sixth Affiliated Hospital, Sun Yat-Sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510610</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Xiao-yan Liang, M.D. &amp; Ph.D.</last_name>
      <phone>020-38048013</phone>
      <email>lxyzy@263.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Jiangsu Province Hospital</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reproductive medical hospital affiliated to Shandong University</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <zip>250001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Wenzhou Medical University</name>
      <address>
        <city>Wenzhou</city>
        <state>Zhejiang</state>
        <zip>325000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tenth People's Hospital of Tongji University</name>
      <address>
        <city>Shanghai</city>
        <zip>200072</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 8, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>December 10, 2018</last_update_submitted>
  <last_update_submitted_qc>December 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Yanhong Deng</investigator_full_name>
    <investigator_title>doctor</investigator_title>
  </responsible_party>
  <keyword>sequential IVM system</keyword>
  <keyword>PCOS</keyword>
  <keyword>infertility</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycystic Ovary Syndrome</mesh_term>
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03773263
org study id: newivf20181206
nct id: NCT03773263
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Oocyte in vitro maturation (IVM) is an artificial reproductive technologies (ART) in which
      cumulus-oocyte complex (COC) are collected at the immature germinal vesicle (GV) stage from
      unstimulated or FSH-primed ovaries and matured in vitro before fertilization. IVM has been
      proposed as a more patient-friendly ART alternative to conventional IVF. Contrary to IVF, IVM
      is the only ART method with no cases of OHSS reported. Hence, patients with PCOS represent
      the major target population for IVM treatment.

      In clinical practice of standard IVM, COCs are aspirated from unstimulated or mildly
      stimulated ovaries and rapidly removed from the meiotic-inhibiting influence of the follicle
      and the follicular fluid. Regardless of in vitro gonadotrophin treatment, oocytes mature
      spontaneously in vitro, hence undergoing meiotic resumption in the absence of the usual
      elaborate cascade of endocrine and paracrine molecular signals that induce maturation in
      vivo. As such, the maturation of oocytes by standard IVM techniques is an artefact that
      compromises subsequent oocyte developmental competence. Numbers of studies have been proposed
      to improve the efficiency of IVM system. Synchronization of meiotic and cytoplasmic
      maturation in antral oocytes arrested at the immature GV-stage remains a major challenge and
      is of fundamental importance for successful fertilization. High intra-oocyte levels of cyclic
      adenosine monophosphate (cAMP), is crucial to maintain the nearly fully-grown oocytes under
      meiotic arrest and to induce oocyte maturation. Research in animal models has indicated that
      a non-physiological drop of cAMP levels in the oocyte results in asynchronous nuclear and
      cytoplasmic maturation.

      Investigators have reported the development of a novel in vitro simulated sequential oocyte
      maturation system. Critical to success of the approach is a pre-IVM phase that generates a
      rapid increase in COC cAMP levels. Secondly, the system utilizes an extended IVM phase
      containing sufficient FSH to drive meiotic induction in the presence of a type-3 PDE
      inhibitor. The high levels of cAMP in the oocyte and the induced nature of oocyte maturation
      mimics some of the key, newly characterized molecular signals that occur during oocyte
      maturation in vivo. Technical and conceptual elements were first developed using mouse,
      bovine and human COCs. Investigators propose a randomized clinical trial to compare a novel
      sequential culture system with the traditional standard oocyte IVM system for PCOS patients.
A multi-center, prospective, randomized clinical trial will be conducted, of comparing
      sequential oocyte IVM system with traditional oocyte IVM system for high OHSS risk PCOS
      patients (AMH>5.6ng/ml). The inclusion criteria will be infertile patients diagnosed by the
      Chinese PCOS criteria, aged below 35 years, and without other known factors interfere
      reproductive or metabolic functions. 300 PCOS patients will be included and randomized into
      either of two groups: group A will administrate sequential oocyte IVM system and group B will
      administrate traditional standard oocyte IVM system. The comparison will be made between
      groups, and both groups are conducted with the HMG administration and embryo vitrification
      freezing. The primary outcome of the study is live birth rate. The embryo development and
      pregnancy outcomes will be followed up and compared between groups.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical pregnancy rate
time frame: 7 weeks gestation
description: The fetal heart beat in an intrauterine gestational sac under ultrasound will be defined as clinical pregnancy.
measure: Oocyte maturation rate
time frame: 30 and 46 hours after oocyte retrieval
description: Oocyte maturation rate (%): number of MII oocytes/ number of oocytes retrieved.
measure: Fertilization rate
time frame: 30 and 46 hours after oocyte retrieval
description: Fertilization rate (%): number of oocytes fertilized/ number of oocytes retrieved.
measure: Cleavage rate
time frame: 24 hours after ICSI
description: Cleavage rate (%): number of cleavages/ number of 2PN embryos.
measure: Day 3 embryo rate
time frame: 72 hours after ICSI
description: Day 3 embryo rate (%): number of Day 3 embryos / number of 2PN embryos.
measure: Good quality embryo rate at cleavage-stage
time frame: 72 hours after ICSI
description: Good quality embryo rate at cleavage-stage (%): number of good quality embryos at cleavage-stage / number of 2PN embryos.
measure: Number of cycles with available embryo
time frame: 72 hours after ICSI
description: Available embryos will be defined as three days after oocyte retrieval with containing more than 4 cells and grade 1 to 2 or containing 4 cells with a grade of 1.
measure: Blastulation rate
time frame: 144 hours after ICSI
description: Blastulation rate (%): number of blastocysts / number of 2PN embryos.
measure: Biochemical pregnancy rate
time frame: 4 weeks gestation
description: A serum β-hCG level above 5 IU/L, which is performed 12 days after embryos transfer, will be defined as biochemical pregnancy.
measure: Implantation rate
time frame: 7 weeks gestation
description: The implantation rate will be defined as the number of gestational sacs seen on the ultrasound divided by the total number of embryos transferred.
measure: Miscarriage rate (at first trimester)
time frame: 28 weeks gestation in maximum
description: Miscarriage at first trimester will be defined by any positive pregnancy test that result in a loss of pregnancy before 12 weeks gestation.
measure: Cumulative pregnancy rate
time frame: 1-2year
description: Cumulative pregnancy rate will be defined as clinical pregnancies with intrauterine fetal heart beat detected divided by the number of retrieval cycles whose embryos are all transferred.
measure: Preterm birth rate
time frame: 1-2year
description: Preterm birth means the baby is born before the 37th week of pregnancy in China.
measure: Newborn birth weight
time frame: 1-2year
description: Newborn birth weight
measure: Neonatal complication rate
time frame: within one month after labor
description: We will collect complications that occur in the neonate including admission to the neonatal intensive care unit (NICU), hospitalization, etc.
measure: Live birth rate
time frame: 1-2year
description: Live birth rate(%): number of live birth/ transferred cycle.
arm group label: sequential oocyte IVM group
arm group type: Experimental
description: From day 7~9 of the menstrual cycle, 225 IU HMG (Menotrophins for Injection) per day will be administrated for 3 days. COCs were removed from aspirated follicular fluid and transferred into HEPES-buffered collection medium. The immature oocytes will be cultured in sequential IVM medium 1 for 6 hours (37℃, 5% CO2), and removed into sequential IVM medium 2 for further cultivation. After 24 and 40 hours cultivation, the mature oocytes will be fertilized by intracytoplasmic sperm injection (ICSI). Two of the D3 embryos (if available) which graded as top-quality embryo will be vitrified and the rest of embryos will be cultivated extendedly. Thawed embryo transfer (TET) will give preference to D3 embryos and carried out with a hormone replacement cycle.
arm group label: traditional oocyte IVM group
arm group type: Active Comparator
description: From day 7~9 of the menstrual cycle, 225 IU HMG (Menotrophins for Injection) per day will be administrated for 3 days. On the day of ovulation, COCs were aspirated and the immature oocytes will be cultured in traditional standard oocyte IVM system (Sage). 30 and 44 hours after cultivation, the maturity of oocytes will be assessed and the mature oocytes will be fertilized by intracytoplasmic sperm injection (ICSI). Two of the D3 embryos (if available) which graded as top-quality embryo will be vitrified and the rest of embryos will be cultivated extendedly. Thawed embryo transfer (TET) will give preference to D3 embryos and carried out with a hormone replacement cycle. If biochemical pregnancy is not achieved, thawed blastocysts transfer will be performed.
intervention type: Drug
intervention name: sequential IVM system
description: The immature oocytes will be cultured in sequential oocyte IVM medium 1 for 6 hours (37℃, 5% CO2). After flushed 3 times, COCs were removed into sequential oocyte IVM medium 2 for further cultivation.
arm group label: sequential oocyte IVM group
intervention type: Procedure
intervention name: intracytoplasmic sperm injection (ICSI)
description: intracytoplasmic sperm injection (ICSI)
arm group label: sequential oocyte IVM group
arm group label: traditional oocyte IVM group
intervention type: Procedure
intervention name: Thawed embryo transfer (TET)
description: Patients administrates oestrogen (Progynova) 3mg twice a day for 10 to 12 days. From the day when endometrium reach a thickness of 8 mm and above, luteal phase support will be given with 10 mg progesterone (Dydrogesterone Tablets,) triple per day and utrogestan (Laboratories Besins International, Paris, France) 0.2g triple per day, until 14 days after embryo transfer.
arm group label: sequential oocyte IVM group
arm group label: traditional oocyte IVM group
intervention type: Drug
intervention name: traditional IVM system
description: COCs were aspirated and the immature oocytes will be cultured in traditional standard oocyte IVM system (Sage). 30 and 44 hours after cultivation, the maturity of oocytes will be assessed.
arm group label: traditional oocyte IVM group
other name: sage
criteria: 
gender: Female
minimum age: N/A
maximum age: 35 Years
healthy volunteers: No
last name: Xiao-yan Liang, M.D. & Ph.D
role: Study Director
affiliation: The Sixth Affiliated Hospital, Sun Yat-Sen University
last name: Xiao-yan Liang, M.D. & Ph.D
phone: 020-38048013
email: lxyzy@263.net
facility: 
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country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Yanhong Deng
investigator title: doctor
mesh term: Polycystic Ovary Syndrome
mesh term: Infertility
mesh term: Syndrome